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Unit III — Calculations

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Q1. Explain in detail the system of weights & measures used in pharmacy including metric, apothecary & avoirdupois with suitable examples

Systems of Weights and Measures in Pharmacy

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A. Metric System (SI System) — Most widely used in modern pharmacy

Note: 1 mL of water = 1 g (practical equivalence used in pharmacy)

• Paracetamol 500 mg tablet
• Syrup volume: 5 mL per dose
• IV fluid: 500 mL Normal Saline

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B. Apothecary System (Older system, still encountered in prescriptions)

• 1 grain = 65 mg (approx. 64.8 mg)
• 1 fluid ounce = 30 mL
• 1 minim = 0.06 mL

• Aspirin gr V = 5 × 65 = 325 mg
• Codeine gr ¼ = 16.2 mg

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C. Avoirdupois System (Used for bulk commodities & commercial trade)

Key difference from apothecary: The pound is 16 oz (avoirdupois) vs. 12 oz (apothecary); but the grain is the same in both systems.

• 1 avoirdupois pound = 454 g
• 1 avoirdupois ounce = 28.4 g

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Interconversion Table (Key equivalents)

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Q2. Describe percentage solutions in detail including types & their method of preparation with numerical examples

Percentage Solutions

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Types of Percentage Solutions

1. % w/v (Weight per Volume)

• Definition: Number of grams of solute dissolved in 100 mL of solution
• Most common type in pharmacy
• Example: 0.9% w/v NaCl (Normal Saline) → 0.9 g NaCl in 100 mL solution

• Amount of glucose = 5% × 500 = 25 g
• Dissolve 25 g glucose in water to make up to 500 mL

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2. % w/w (Weight per Weight)

• Definition: Grams of solute per 100 g of solution (mixture)
• Used for semisolids (ointments, creams, pastes)
• Example: 2% w/w Salicylic acid ointment → 2 g salicylic acid in 100 g ointment

• Sulphur required = 5% × 200 = 10 g
• Ointment base = 190 g
• Mix 10 g sulphur with 190 g ointment base

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3. % v/v (Volume per Volume)

• Definition: mL of liquid solute per 100 mL of solution
• Used for liquid–liquid preparations
• Example: 70% v/v ethanol → 70 mL absolute ethanol in 100 mL solution

• 95 × V₁ = 70 × 1000
• V₁ = 736.8 mL of 95% ethanol; dilute to 1000 mL with water

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4. % v/w (Volume per Weight) — rarely used

• mL of liquid per 100 g of preparation

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Dilution of Percentage Solutions

• 10 × V₁ = 2 × 200 → V₁ = 40 mL of 10% stock + 160 mL water

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Q3. What is proof spirit? Explain the concept of over-proof and under-proof. Describe the method used to adjust alcoholic strength — with examples

Proof Spirit

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Over-proof Spirit

• Stronger than proof spirit (contains more alcohol than 57.1% v/v)
• Example: "30° over proof" (OP) = 30% more alcohol than proof spirit
• Calculation: % v/v = 57.1 + (30 × 0.571) = 57.1 + 17.13 = 74.23% v/v

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Under-proof Spirit

• Weaker than proof spirit (less than 57.1% v/v)
• Example: "30° under proof" (UP) = 30% less alcohol than proof spirit
• Calculation: % v/v = 57.1 − (30 × 0.571) = 57.1 − 17.13 = 39.97% v/v

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Dilution of Alcohol — Pearson's Square / Alligation Method

       90
           \      (50-20) = 30 parts of 90%
    50
           /      (90-50) = 40 parts of 20%
       20
Total = 70 parts

• Parts of 90% = 30 parts
• Parts of 20% = 40 parts

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Q4. Describe the dilution method in detail & explain how it is used in pharmaceutical calculations with suitable problems

Dilution Method

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A. Dilution of Solutions

• C₁ = Initial concentration, V₁ = Initial volume
• C₂ = Final concentration, V₂ = Final volume

• 6 × V₁ = 2 × 500
• V₁ = 166.7 mL of 6% stock; add water to 500 mL

• 5 × V₁ = 0.9 × 1000
• V₁ = 180 mL stock; dilute to 1000 mL

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B. Alligation Medial (Weighted Average)

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C. Alligation Alternate

95 → (70-45) = 25 parts of 95%
45 → (95-70) = 25 parts of 45%
Ratio = 25:25 = 1:1

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D. Stock Solutions

• 1:50 = 2% and 1:200 = 0.5%
• C₁V₁ = C₂V₂ → 2 × V₁ = 0.5 × 30 → V₁ = 7.5 mL

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Q5. Define isotonic solutions & explain the different methods used to adjust isotonicity (sodium chloride equivalent, freezing point depression method) with examples

Isotonic Solutions

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Methods to Adjust Isotonicity

1. Sodium Chloride Equivalent Method (E value method)

1. Calculate mass of NaCl equivalent = E × quantity of drug
2. Subtract from 0.9 g per 100 mL (total NaCl needed for isotonicity)
3. Add the remaining NaCl to achieve isotonicity

• E value for cocaine HCl = 0.16
• NaCl equivalent = 0.16 × 1 g = 0.16 g
• NaCl already "used" by drug = 0.16 g
• Additional NaCl needed = 0.9 − 0.16 = 0.74 g
• Answer: Dissolve 1 g cocaine HCl + 0.74 g NaCl in water to 100 mL

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2. Freezing Point Depression (FPD) Method

• FPD of 1% atropine sulfate = 0.073°C
• Additional NaCl = (0.52 − 0.073) / 0.576 = 0.447/0.576 = 0.776 g per 100 mL
• Answer: Dissolve 1 g atropine sulfate + 0.776 g NaCl in water to 100 mL

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3. White-Vincent Method (for ophthalmic/parenteral solutions)

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Unit IV — Powders & Other Forms

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Q1. Define powders and describe their classification, advantages & disadvantages as a dosage form

Definition

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Classification

A. By Use:

B. By Composition:

C. By Particle Size (BP Classification):

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Advantages of Powders

1. Flexible dosing — dose can be adjusted easily
2. Easy to swallow for patients unable to take tablets (elderly, children)
3. Rapid absorption — large surface area promotes dissolution
4. Stable — no liquid stability issues
5. Economical — simple manufacturing process
6. Versatile — can be used internally or externally

Disadvantages of Powders

1. Unpleasant taste difficult to mask
2. Hygroscopic powders may absorb moisture (stability issues)
3. Inaccurate dosing with bulk powders
4. Not suitable for volatile, deliquescent, or efflorescent drugs
5. Incompatibilities (eutectic mixtures) may occur on mixing
6. Time-consuming for the patient (measuring, dissolving)
7. Not suitable for potent drugs (narrow therapeutic index)

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Q2. Explain the methods of preparation of simple and compound powders including mixing techniques used for dispensing

General Principles of Powder Mixing

Equipment: Mortar and pestle, spatula, pill tile

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Methods of Mixing

1. Trituration

• Rubbing/grinding particles together in a mortar
• Reduces particle size and ensures uniform mixing
• Used for most dry powders

2. Geometric Dilution

• Used when a potent drug is present in small amounts mixed with a large amount of diluent
• Procedure:
  1. Place drug in mortar
  2. Add equal volume of diluent, mix thoroughly
  3. Add another equal volume of diluent, mix again
  4. Continue doubling until all diluent is incorporated
• Example: Mixing 50 mg codeine in 10 g lactose

3. Spatulation

• Mixing powders on a pill tile with a spatula
• Used for eutectic mixtures (e.g., aspirin + phenacetin) where heat from mortar grinding may cause melting
• Does not reduce particle size

4. Sifting

• Powders are passed through sieves
• Ensures uniform particle size and good mixing of light powders

5. Tumbling

• Used in large-scale manufacturing (V-blender, double cone blender)
• Containers are rotated for blending

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Preparation of Simple Powder

• Weigh: 10 × 300 mg = 3000 mg (3 g) aspirin
• Triturate in mortar
• Divide into 10 equal papers (each weighing ~300 mg)
• Wrap in separate paper packets (wax paper)

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Preparation of Compound Powder

• Chalk – 125 g
• Cinnamon – 60 g
• Nutmeg – 30 g
• Sucrose – 500 g
• Triturate each ingredient separately; combine using geometric dilution; pass through 250 μm sieve

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Special Considerations in Powder Mixing

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Q3. Write a detailed note on insufflations and dusting powders including their preparation, use & precautions

A. Insufflations

Uses:

• Nasal insufflations: for nasal infections, decongestants
• Aural (ear) insufflations: for external ear canal infections
• Pharyngeal (throat) insufflations
• Vaginal insufflations

Preparation:

• Use very finely powdered ingredients (micronized if needed)
• Mix using geometric dilution
• Pass through a 125 μm sieve (No. 120)
• Package in a suitable insufflator or capsule for use with DPI (Dry Powder Inhaler)

• Boric acid (finely powdered) 3 g
• Starch 97 g
• Pass through sieve; fill in insufflator

Precautions:

• Should be sterile if used for wounds or surgical cavities
• Must be free from irritants
• Should not be inhaled accidentally (can cause respiratory harm if coarse)
• Store in airtight containers
• Not suitable for moist, weeping lesions

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B. Dusting Powders

Properties:

• Smooth feel (slip)
• Good covering power
• Absorbent and/or antiseptic
• Non-irritant

Common Bases:

Types of Dusting Powders:

1. Absorbent – talc, starch, kaolin → for moist skin/intertrigo
2. Antiseptic – boric acid, zinc oxide → for infected wounds
3. Antifungal – undecylenic acid + zinc undecylenate → athlete's foot
4. Protective – zinc stearate, titanium dioxide → skin protection

• Zinc oxide 25 g
• Starch 25 g
• Talc 50 g
• Mix and pass through 180 μm sieve

Precautions for Dusting Powders:

• Must NOT be used on raw/bleeding wounds (may cause granuloma)
• Must be non-irritant and non-toxic
• Must be sterile if applied to surgical wounds
• Containers must be well-closed to avoid contamination
• Talc-based powders should not be inhaled (risk of talcosis)
• Must not contain gritty particles

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Q4. What are eutectic powders and explosive powders? Explain their characteristics with examples and methods to handle them safely

A. Eutectic Powders

Characteristics:

• When mixed, solids liquefy/become sticky or pasty
• The eutectic temperature is lower than the melting point of either component alone
• Creates formulation problems in powders

Common Eutectic Combinations:

Methods to Handle Eutectic Mixtures:

1. Spatulation on a cool pill tile (avoid heat from friction in mortar)
2. Add an absorbent/adsorbent — light magnesium carbonate, magnesium oxide, or light kaolin — to absorb the liquid and keep the mixture powdery
3. Dispense the eutectics in separate papers and instruct patient to mix just before use
4. Convert one component to a less reactive form

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B. Explosive Powders

Characteristics:

• Release large amounts of energy on mixing
• May be triggered by friction, heat, or impact
• Extremely hazardous in pharmaceutical dispensing

Common Explosive Combinations:

Methods to Handle Explosive Combinations:

1. Never mix — dispense in separate containers
2. Use alternatives (substitute the problematic component)
3. Dilute each ingredient separately before combining (with inert excipient)
4. Provide separate labelling and dispensing instructions
5. Wear appropriate PPE; work in fume cupboard
6. Never use glass mortar for explosive combinations (use porcelain)
7. Clearly label "DANGEROUS — DO NOT MIX"

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Q5. Describe the preparation formula and use of tooth powders, mouth powders & effervescent powders and granules

A. Tooth Powders (Dental Powders)

• Precipitated calcium carbonate – 60 g (abrasive)
• Sodium bicarbonate – 20 g (mild alkaline)
• Sodium chloride – 10 g (antiseptic)
• Peppermint oil – 2 mL (flavour)
• Saccharin sodium – 0.5 g (sweetener)
• Make to 100 g with light kaolin

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B. Mouth Powders

• Sodium bicarbonate – 20 g
• Borax (sodium borate) – 10 g
• Sodium chloride – 5 g
• Peppermint oil – 0.5 mL
• Saccharin – 0.3 g

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C. Effervescent Powders & Granules

• Masks unpleasant taste
• Improves patient compliance
• CO₂ speeds gastric emptying and absorption
• Antacid effect (with bicarbonate)

• Citric acid (most common)
• Tartaric acid
• Both may be used together (1 part tartaric + 2 parts citric → better texture)

Reaction:

Citric acid + NaHCO₃ → Sodium citrate + H₂O + CO₂↑

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• Sodium potassium tartrate (Rochelle salt) – 7.5 g
• Sodium bicarbonate – 2.5 g

• Tartaric acid – 2.5 g

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• Citric acid – 25 g
• Tartaric acid – 45 g
• Sodium bicarbonate – 60 g
• Sugar (powdered) – 200 g
• Flavour – q.s.

1. Wet method: Mix acids with NaHCO₃; use a small amount of water/alcohol as binding liquid; pass through sieve (4 mm); dry at 37°C in oven
2. Dry heat method (Fusion method): Citric acid (monohydrate) provides its own water of crystallisation; mix with NaHCO₃; heat gently to cause slight dampening; granulate; dry rapidly
3. Dry granulation: Use dry binders; compress then break into granules

• Prepare in low humidity (<25% RH) conditions
• Use moisture-proof packaging (sealed glass bottles, foil sachets)
• Perform in small batches rapidly

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Sources: Based on standard Pharmaceutical Sciences textbooks — Cooper & Gunn's Dispensing for Pharmaceutical Students; Remington's Pharmaceutical Sciences; Aulton's Pharmaceutics: The Design and Manufacture of Medicines; Indian Pharmacopoeia.

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UNIT – VII: SUPPOSITORIES & PESSARIES

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Q1. Define Suppository & Pessary & discuss their Advantages & Disadvantages as pharmaceutical dosage forms

Definitions

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Advantages of Suppositories & Pessaries

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Disadvantages of Suppositories & Pessaries

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Q2. Classify the types of Suppositories & explain their properties, selection criteria & examples

Classification of Suppositories

A. Based on Route of Administration

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B. Based on Base (Most Important Classification)

1. Fatty / Oleaginous Bases (Lipophilic)

• Melting point: 30–36°C (just below body temperature)
• Wide melting range for ease of manufacture
• No irritation to mucosa
• Compatible with most drugs
• Contracts on cooling (facilitates removal from mold)

a) Theobroma Oil (Cocoa Butter)

• Most classical base; natural fat from cacao seeds
• Melting point: 30–36°C — melts quickly in rectum
• Exists in 4 polymorphic forms (α, β, β', γ)
• β-form is most stable (MP 34–35°C)
• Disadvantage: Polymorphism — if overheated, unstable forms (MP 18–23°C) form → won't set at room temp
• Disadvantage: Rancidity; doesn't absorb aqueous solutions well
• Example: Glycerin suppositories, bismuth suppositories

b) Hard Fat (Adeps Solidus / Witepsol / Suppocire)

• Semi-synthetic glycerides; hydrogenated vegetable oils
• Witepsol H15: MP 33.5–35.5°C — most commonly used today
• Advantages over cocoa butter: No polymorphism, good water absorption, stable, odourless
• Witepsol W35: higher water absorption capacity
• Example: Widely used in commercial suppository manufacture

c) Synthetic Bases (Massa Estarinum, Dehydag)

• Improved glycerides; predictable melting behaviour

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2. Water-Soluble / Water-Miscible Bases (Hydrophilic)

a) Glycerinated Gelatin (Glycerogelatin)

• Gelatin + glycerin + water
• Used mainly for pessaries (vaginal)
• Softens and dissolves slowly → prolonged action
• Formulation: Gelatin 14%, Glycerin 70%, Water 16%
• Disadvantage: May cause dehydration of rectal mucosa (osmotic effect of glycerin)

b) Polyethylene Glycol (PEG / Macrogol) Bases

• Available in various molecular weights: PEG 1000, 1540, 4000, 6000
• Mixed in appropriate ratios to give desired hardness and dissolution rate
• Does NOT melt at body temperature — dissolves in rectal fluid
• Advantages: stable, no refrigeration required, no polymorphism
• Disadvantages: May irritate mucosa; hygroscopic (absorbs moisture from mucosa causing discomfort); incompatible with many drugs
• Example: Chlorpromazine suppositories (PEG base)

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3. Emulsifying Bases

• Can absorb water and emulsify aqueous solutions
• e.g., Suppocire AM (with emulsifier)

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Properties Required of an Ideal Suppository Base

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Selection Criteria for Suppository Base

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Q3. Describe the methods of preparation of Suppositories including hand moulding, fusion moulding & compression methods

I. Hand Rolling / Hand Moulding Method

1. Weigh cocoa butter and grate finely
2. Triturate drug with a portion of cocoa butter in mortar
3. Add remaining cocoa butter and knead into a uniform mass (plastic mass at room temp)
4. Roll into a cylinder on a pill tile
5. Cut into required number of pieces
6. Shape each piece into a cone/torpedo shape by hand or with a board

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II. Fusion / Moulding Method (Most Common — Official Method)

1. Calculate amount of base required using displacement value
2. Melt the base in a water bath at minimum temperature (do NOT overheat; max 5°C above melting point)
3. Incorporate drug:
   • Water-soluble drugs: dissolve in minimum water and incorporate as fine emulsion
   • Insoluble drugs: triturate to fine powder and incorporate by geometric levigation
4. Lubricate molds with liquid paraffin or soap spirit (not needed for Witepsol which contracts well)
5. Pour the melt into molds slightly above the level (overfill by ~10% as it shrinks on setting)
6. Cool at room temperature or in refrigerator (not below 5°C suddenly)
7. Trim excess with a warm spatula
8. Unmold and wrap in foil
9. Pack in labeled containers; store at 2–8°C

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III. Compression Moulding Method

1. Mix powdered base (cocoa butter or hard fat) with finely powdered drug
2. Load the suppository press/machine
3. Apply pressure to compress the mixture directly into the mold
4. Eject from mold

• No heating — suitable for thermolabile drugs
• No risk of polymorphism
• Faster for industrial production

• Air entrapment → porous suppositories
• Not suitable for all bases
• Requires special equipment

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Calculations in Fusion Method

Amount of base = (Total wt of blank suppository × No.) − (DV calculation correction)

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Special Considerations During Preparation

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Q4. What is Displacement Value? Explain its importance & describe the method of calculation with a suitable example

Definition

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Importance of Displacement Value

1. Volume of mold is fixed — a mold holds a fixed volume regardless of what fills it.
2. If a drug is denser than the base, the same volume weighs more. Simply replacing base with an equal weight of drug would overflow the mold.
3. Without displacement value correction, suppositories will be incorrectly dosed — either underfilled or overfilled.
4. Ensures each suppository contains the exact prescribed dose of drug.
5. Critical for drugs with high dose (>100 mg per suppository) where the drug displaces a significant volume of base.

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Formula

• n = number of suppositories
• W = weight of blank suppository (suppository made with base alone)
• d = weight of drug per suppository
• DV = displacement value of the drug

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Common Displacement Values

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Worked Example

• Zinc oxide: 5.6 g
• Cocoa butter: 26.81 g
• Total mass: 5.6 + 26.81 = 32.41 g ÷ 14 = 2.315 g per suppository ✓ (fills mold correctly)

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Another Example

• Total drug = 10 × 0.5 = 5 g
• Displacement = 5 / 1.5 = 3.33 g
• Total base required = (10 × 2) − 3.33 = 20 − 3.33 = 16.67 g cocoa butter

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Q5. Describe the evaluation tests for Suppositories & Pessaries including physical, chemical & performance parameters

Evaluation of Suppositories & Pessaries

A. Physical Tests

1. Appearance & Uniformity

• Should be smooth, uniform in color, free from surface cracks or pitting
• Visual inspection

2. Weight Uniformity (BP/IP)

• Weigh 20 suppositories individually
• Calculate mean weight
• Limit: Not more than 2 suppositories should deviate by more than ±5% from mean weight

3. Hardness / Breaking Strength

• Suppository is subjected to increasing axial load
• Equipment: Suppository hardness tester (Erweka or similar)
• Acceptance: Should not break under normal handling conditions
• Typical value: >1.8 kg (Kieffer test)

4. Melting Range Test / Softening Time

• IP/BP test: Place suppository in a glass tube immersed in water bath at 37°C
• Measure time taken for suppository to soften and flow
• Acceptance: Should melt/soften within 30 minutes at 37°C (IP)
• For fatty bases — melting; for hydrophilic bases — dissolution time measured

5. Liquefaction Time (Melting Time)

• Place in water at 37 ± 0.5°C
• Time recorded until complete liquefaction
• Limit: Not more than 30 minutes

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B. Chemical Tests

1. Assay of Active Ingredient

• Extract drug from base using appropriate solvent
• Determine drug content by UV spectrophotometry, HPLC, or titrimetry
• Acceptance: 90–110% of labeled claim (BP)

2. Uniformity of Drug Content

• 10 suppositories individually assayed
• Results should be within 85–115% of labeled amount
• Not more than 1 suppository outside 75–125% range

3. pH Determination (for water-soluble bases)

• Dissolve in water; measure pH
• Should be appropriate for mucosal tissue (rectal pH ~7; vaginal pH ~4.5)

4. Water Content / Moisture Content

• Determined by Karl Fischer titration
• Important to prevent hydrolysis

5. Drug-Base Compatibility

• Compatibility studies: visual, DSC (Differential Scanning Calorimetry), FTIR

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C. Performance / Biopharmaceutical Tests

1. Dissolution Test

• Apparatus: Rotating basket, paddle, or specialized dissolution apparatus (PhEur dialysis membrane method)
• Suppository placed in vessel with simulated rectal fluid at 37°C
• Samples taken at intervals; drug content measured by UV/HPLC
• Purpose: Predicts drug release rate

2. Drug Release Test (In-vitro Release)

• Dialysis membrane method: suppository placed in dialysis bag, immersed in dissolution medium
• Measures diffusion of drug across membrane
• Important for sustained-release or local-action suppositories

3. Rupture / Disintegration Test (for hard gelatin shell pessaries)

• IP test: Disintegrate in simulated vaginal fluid at 37°C within 30 minutes

4. Spreading Test (for pessaries and soft preparations)

• Measures area of spread at body temperature
• Important for vaginal creams/soft pessaries

5. Microbial Limit Tests (for non-sterile preparations)

• Total aerobic microbial count, absence of pathogens
• Stricter requirements for vaginal/urethral routes

6. Sterility Test (for sterile suppositories)

• Required for preparations intended for wounds, post-surgical use

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Summary Table

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UNIT – VIII: GALENICALS (EXTRACTIVE PREPARATIONS)

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Q1. Define Galenicals & discuss the various Extraction Processes used in their preparation including Maceration & Percolation

Definition of Galenicals

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General Principles of Extraction

• Marc: The exhausted drug residue after extraction
• Menstrum: The solvent used for extraction
• Percolate: The liquid that flows out of the percolator
• Miscella: The extract solution

1. Particle size of drug (finer → greater surface area → better extraction)
2. Nature of solvent (polarity must match solutes)
3. Temperature (higher → greater diffusion)
4. Time (longer → more complete extraction)
5. Drug:solvent ratio
6. pH of menstrum
7. Agitation/stirring

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Extraction Processes

1. MACERATION

• Simple maceration: Drug + solvent, stand with occasional shaking
• Double maceration: Drug macerated twice with fresh solvent; extracts combined
• Digestion: Maceration at elevated temperature (40–60°C) using a digestor
• Cold maceration: At room temperature

1. Macerate the coarsely powdered drug in 3/4 of the specified menstrum for 7 days
2. Strain the mixture; press the marc
3. Add remaining menstrum to marc; stand for 1 day
4. Strain again; combine both liquids
5. Allow to stand for 3 days; filter

• Simple equipment
• No special apparatus required
• Suitable for drugs that yield their constituents readily to cold menstruum

• Time-consuming (days)
• Incomplete extraction
• Not suitable for hard, woody drugs
• Solvent may not be fully saturated

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2. PERCOLATION

• Simple percolation
• Repercolation: Drug divided into portions; percolate from one portion used to percolate next
• Forced percolation: Under pressure

1. Prepare drug: Reduce to moderately coarse powder (355–710 μm)
2. Moisten drug: Add 3/4 of menstrum; stand 4 hours for swelling
3. Pack percolator: Place pledget of cotton at bottom; introduce moist drug in layers (firmly but not too tightly packed)
4. Add remaining menstrum on top
5. Allow to macerate for 24 hours (closed stopcock)
6. Open stopcock; collect percolate at 1–3 mL/min (slow rate for complete extraction)
7. Add more menstrum as needed; collect required volume
8. Adjust to volume with menstrum

• More complete extraction than maceration
• Continuous process; fresh solvent always available
• Suitable for large-scale production
• Concentration gradient maintained

• Special apparatus (percolator) needed
• Drug must not swell excessively (would block percolator)
• Cannot be used for gummy, mucilaginous drugs
• Time-consuming for hard drugs

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3. Other Extraction Methods

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Q2. Describe the principle & method of equipment used in Maceration & Percolation

Maceration — Equipment & Method

Equipment:

• Macerating vessel: Wide-mouthed glass jar, stainless steel vat, or earthenware pot with tight-fitting lid
• Stirrer: Mechanical or manual
• Strainer/Coarse sieve
• Filter press or Buchner funnel (for final filtration)
• Press (Hydraulic): For pressing marc

Detailed Method (Official IP/BP):

• Reduce drug to coarse powder (BP: Moderately coarse; sieve 710 μm)
• Prepare menstrum (e.g., 60% ethanol for most tinctures)

• Transfer powdered drug to vessel
• Add ¾ of total menstrum volume
• Close tightly; agitate twice daily for 7 days (official)
• Temperature: Room temperature (15–25°C) unless digestion specified

• After 7 days, strain through coarse cloth
• Transfer marc to hydraulic press; press to recover residual extract
• Combine strained liquid + pressed liquid

• Add remaining ¼ menstrum to marc
• Stand 24–48 hours; strain again

• Combined extracts allowed to stand 3 days in cool place
• Carefully decant or filter through filter paper
• Adjust to required volume

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Percolation — Equipment & Method

Equipment: The Percolator

1. Cylindrical percolator — simple, used in pharmacy practice
2. Conical percolator — wider at top, tapers at bottom; easier packing
3. Industrial percolator — large stainless steel vessel with jacket for temperature control

• Body (cylindrical/conical) — holds drug
• Stopcock/valve at bottom — controls flow rate
• Pledget of cotton/glass wool at bottom — supports drug, allows liquid through
• Perforated plate/grid (in some designs)
• Inlet at top for solvent addition

Detailed Method:

• Powder drug to specified grade (moderately coarse for most; coarse for resinous drugs)

• Mix drug powder with ¾ of specified menstrum in a closed vessel
• Allow to stand 4–6 hours to allow swelling of drug particles
• This prevents excessive swelling inside percolator which could block it

• Close the stopcock
• Place a pledget of cotton at the bottom outlet
• Introduce moistened drug in small portions
• Each portion packed firmly (but not too tightly) with a piston/rammer
• Surface should be level; add a disc of filter paper on top to prevent disturbance by solvent

• Add sufficient menstrum to just cover drug surface
• Close stopper; allow to macerate for 24 hours

• Open stopcock; allow to drip at 1–3 mL/min (slow percolation for tinctures)
• As percolate drips out, continuously add fresh menstrum to maintain level above drug
• Collect percolate in a measuring cylinder

• Collect required volume (usually 900–1000 mL from 100 g drug for a 1:10 tincture)
• Reserve the first 3/4 of percolate ("first percolate") which is the strongest fraction

• Allow percolate to stand 2–3 days in cool, dark place
• Filter; adjust to final volume

• Too fast → incomplete extraction
• Too slow → economically impractical

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Q3. Explain the preparation of Infusions & Decoctions including their advantages & limitations

A. INFUSIONS

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Method of Preparation (IP/BP Method)

1. Weigh the drug; reduce to appropriate particle size (coarse powder or broken pieces)
2. Place drug in an earthenware/glass vessel
3. For cold infusion: Pour cold water; macerate for 30 minutes with frequent agitation; strain
4. For hot infusion: Bring water to boiling; pour over drug; cover; stand for 15 minutes; strain while hot; squeeze residue; filter
5. Adjust volume to specified amount with cold water
6. Use within 24 hours (no preservative — highly susceptible to microbial contamination)

• Gentian infusion (Compound): Gentian root 5 g, lemon peel, ginger — in 100 mL
• Senna infusion: Senna leaves 5 g + water 100 mL
• Quassia infusion (concentrated): 8× the standard strength; diluted 1:8 before use

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Advantages of Infusions:

1. Simple and rapid preparation
2. Large amounts of water-soluble constituents extracted efficiently
3. Suitable for soft vegetable drugs (leaves, flowers) that yield easily
4. Patient can prepare at home (e.g., herbal teas)
5. No alcohol — suitable for patients avoiding alcohol

Limitations / Disadvantages:

1. Prepared freshly — short shelf-life (24 hours); prone to rapid microbial growth
2. Starch, albumin, mucilage also extracted (impurities)
3. Not suitable for hard, woody drugs (insufficient extraction)
4. Cannot extract resinous/oil-soluble constituents
5. Bulky preparations — inconvenient storage and transport
6. No standardization possible for concentrated infusions without assay

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B. DECOCTIONS

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Method of Preparation:

1. Coarsely powder or break up the drug (roots, bark, woody stems)
2. Place drug + water (slightly more than required volume, to account for evaporation) in a covered vessel
3. Boil for 15 minutes with occasional stirring
4. Strain while still hot through muslin/cloth
5. Press marc; add strained liquid to pressing
6. Allow to cool; add cold water to adjust to required volume
7. Filter if necessary

• Decoction of Cinchona bark (quinine extraction)
• Decoction of Cascara sagrada bark
• Decoction of Sarsaparilla root
• Senega decoction (expectorant)

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Advantages of Decoctions:

1. Efficient extraction of thermostable constituents from hard drugs
2. Boiling water breaks down cell walls → releases tightly bound constituents
3. No solvent cost (water only)
4. Familiar household preparation method
5. Suitable for barks, roots, seeds (dense tissues)

Limitations / Disadvantages:

1. Not suitable for thermolabile constituents (heat destroys volatile oils, alkaloids, glycosides)
2. Short shelf-life — 24 hours without refrigeration (bacterial growth)
3. Cannot extract non-polar/resinous constituents
4. Starch gelatinizes on boiling → filter difficulty
5. Colour, tannins co-extracted (astringent taste)
6. Evaporation during boiling makes standardization difficult
7. Not suitable for gummy/mucilaginous drugs (viscous masses formed)

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Comparison: Infusion vs. Decoction

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Q4. Discuss the principle & method of preparation of Tinctures including official & unofficial methods with suitable examples

Definition

• Potent drug tinctures: 1:10 (10 g drug/100 mL) — e.g., Tincture Belladonna, Tincture Digitalis
• Non-potent drug tinctures: 1:5 (20 g drug/100 mL) — e.g., Tincture Gentian, Tincture Ginger

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Official Methods of Preparation

Method A — Maceration (IP Official)

1. Powder drug to moderately coarse grade
2. Moisten with 3/4 of menstrum; macerate in closed vessel with occasional shaking for 7 days at room temperature
3. Strain; press marc
4. Add remaining menstrum to marc; macerate 1–2 days; strain
5. Combine liquids; allow to stand 3 days in cool place
6. Carefully decant or filter; adjust to required volume
7. Assay if required; adjust strength

• Gentian root (powder) 10 g
• Dried orange peel 2.5 g
• Cardamom 2.5 g
• Ethanol 60% q.s. to 100 mL
• Macerate 7 days; strain; adjust

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Method B — Percolation (IP Official)

1. Powder drug to moderately coarse grade
2. Moisten with ¾ menstrum; pack in percolator after 6 hours imbibition
3. Macerate 24 hours in closed percolator
4. Percolate slowly (1–3 mL/min); add menstrum continuously
5. Collect first 850 mL of percolate separately ("first percolate")
6. Continue percolating until drug is exhausted; collect as "second percolate"
7. Evaporate second percolate under vacuum to small volume; add to first percolate
8. Adjust to 1000 mL with menstrum

• Belladonna leaf powder 100 g in 1000 mL 70% ethanol
• Percolation method; assay for total alkaloids (0.027–0.033% w/v)

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Method C — Solution Method (Non-official / Simple)

• Simply dissolve the substance in specified strength ethanol
• Example: Tincture Iodine (Official compound: iodine + potassium iodide in alcohol)

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Important Official Tinctures

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Quality Standards for Tinctures:

• Appearance: Clear, slightly turbid on standing (precipitate on cooling)
• Alcohol content: As specified by IP/BP (usually 45–90% v/v)
• Assay: Active constituent within specified limits
• Storage: Cool, dark place; well-closed amber bottles; away from heat sources (flammable)

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Q5. Write a detailed note on the preparation of Spirits & Extracts including their types, methods & pharmaceutical use

A. SPIRITS (Spiritus)

1. Simple Spirit (Aromatic Spirit)

• Solution of single volatile oil in strong ethanol
• Example: Spirit of Peppermint (Spiritus Menthae Piperitae IP) — Peppermint oil 10 mL in 100 mL 90% ethanol

2. Compound Spirit

• Mixture of two or more volatile oils
• Example: Compound Spirit of Ammonia (Spiritus Ammoniae Aromaticus) — Ammonia solution + aromatics in ethanol

3. Medicated Spirits

• Volatile chemical dissolved in ethanol
• Example: Spirit of Camphor — Camphor 10 g dissolved in 100 mL 90% ethanol

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Methods of Preparation:

• Dissolve volatile oil/substance directly in measured quantity of specified strength ethanol
• Mix well; filter through moistened filter paper
• Example: Spirit of Chloroform: Chloroform 5 mL + ethanol 90% to 100 mL

• Drug soaked in alcohol; distilled
• Distillate (containing volatile oil) collected
• Example: Spirit of Juniper (Spiritus Juniperi) — juniper berries distilled with ethanol

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Official Spirits (IP/BP):

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B. EXTRACTS (Extracta)

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Method of Preparation of Liquid Extract (Fluid Extract) — IP Method

1. Reduce drug to moderately coarse powder
2. Moisten with ¾ menstrum; pack into percolator; macerate 24 hours
3. Percolate slowly; collect first 3/4 volume (= 750 mL from 1000 g drug) separately — this is the "reserved fraction"
4. Continue percolation; collect remaining percolate; evaporate under vacuum (45–60°C) to small volume
5. Cool; combine with reserved fraction
6. Adjust to final volume (1000 mL for 1000 g drug = 1:1)
7. Allow to stand; filter

• Cascara bark 1000 g → 1000 mL fluid extract
• Menstrum: 70% ethanol
• Use: Laxative

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Method of Preparation of Dry Extract:

1. Prepare concentrated percolate/macerate
2. Evaporate under reduced pressure at 40–60°C (avoid degradation)
3. Dry in vacuum oven at 40°C to <5% moisture
4. Powder the dry mass (mill/trituration)
5. Standardize with assay; adjust with diluent (lactose, starch) to correct strength

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Pharmaceutical Uses:

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UNIT – IX: PHARMACEUTICAL CALCULATIONS & SURGICAL AIDS

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Q1. Explain the importance of Pharmaceutical Calculations in Pharmacy Practice & discuss various types with suitable examples

Importance of Pharmaceutical Calculations

1. Patient safety: Incorrect dose calculation can lead to toxicity or therapeutic failure
2. Accurate compounding: Ensures correct quantity of each ingredient
3. Reconstitution: Calculating correct diluent volumes
4. Dose adjustment: For pediatric, geriatric, renal/hepatic impaired patients
5. IV infusion rates: Critical in ICU/anaesthesia
6. Standardization: Ensures product quality and batch reproducibility
7. Billing and stock management: Accurate dispensing reduces waste

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Types of Pharmaceutical Calculations

1. Percentage & Ratio Strength Calculations

• 1:5000 = 1 g in 5000 mL = 0.02% w/v

• 0.5% = 0.5 g/100 mL = 5 g/1000 mL → 1.25 g = 1250 mg

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2. Dilution & Concentration Calculations (C₁V₁ = C₂V₂)

• 10 × V₁ = 2.5 × 200 → V₁ = 50 mL; add 150 mL water

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3. Alligation (Mixing calculations)

• 50-30 = 20 parts of 70%
• 70-50 = 20 parts of 30%
• Ratio = 1:1

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4. Doses & Dose Calculations

• Child's dose = (40/150) × 500 = 133 mg

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5. IV Infusion Rate Calculations

• = (500 × 15) / 240 = 31.25 ≈ 31 drops/min

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6. Electrolyte Calculations (mEq)

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7. Displacement Value (see Unit VII Q4)

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8. Alcohol Calculations (Proof Spirit)

• 100° proof = 57.1% v/v
• 75° proof = 75 × 0.571 = 42.8% v/v

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9. Specific Gravity Calculations

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10. Powder Fineness & Sieve Calculations

• Sieve number refers to mesh openings
• Sieve No. 85 = 180 μm opening; fine powder
• If 5% retained on Sieve 85 — not a fine powder

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Q2. Define Surgical Dressings & describe their Preparation, Properties & Use in detail

Definition

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Classification of Surgical Dressings

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A. Absorbent Cotton (Cotton Wool) — IP/BP

1. Raw cotton (linters) cleaned and defatted with dilute NaOH (mercerization)
2. Bleached with chlorine/hypochlorite (removes natural oils, waxes, colouring)
3. Washed thoroughly with water
4. Dried and formed into rolls/pads
5. Sterilized (if for wound use)

• White, soft, flexible fibres
• Absorbs water readily (≥23 times its weight — IP specification)
• Free from fatty matter (sink test: dip in water → must sink within 10 sec)
• pH of aqueous extract: 6–8
• Absorbency, sterility, absence of heavy metals, fluorescence

• Wound dressing and padding
• Cleansing wounds
• Applying medications
• Surgical padding

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B. Absorbent Gauze (Gauze BP/IP)

1. Woven from absorbent cotton yarn
2. Bleached and defatted (same as cotton wool)
3. Cut and rolled into bandage rolls or cut pads
4. Sterilized by autoclave (121°C, 15 min)

• Thread count: Not less than 44 threads/cm in warp; 30 in weft
• Absorbency: Sinks in water within 10 seconds
• Free from starch and fatty matter

• Plain absorbent gauze — general wound dressing
• Petrolatum gauze (Tulle Gras) — gauze impregnated with white soft paraffin; non-adhesive dressing for skin grafts, burns
• Zinc oxide medicated gauze — used in leg ulcers
• Iodoform gauze — antiseptic packing for cavities

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C. Lint (Absorbent Lint IP)

• Smooth side applied away from wound
• Used for absorbing wound exudate

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Properties Required of All Surgical Dressings

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Q3. Write a detailed note on Absorbable Gelatin Sponge including its preparation, properties & application

Definition

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Preparation (Manufacturing)

1. Gelatin solution: Prepare concentrated solution of purified gelatin (porcine skin gelatin) in sterile water
2. Aeration: Beat the gelatin solution vigorously to incorporate air bubbles (forming foam)
3. Pouring: Pour the foam into molds (sheet form)
4. Drying: Dry the foamed gelatin to form a rigid sponge
5. Cross-linking (optional): Gelatin may be cross-linked with formaldehyde vapour to control resorption rate
6. Cutting: Cut into standard sizes (sheets, strips, cubes)
7. Sterilization: Sterilize by dry heat (130°C for 3 hours) — NOT by autoclave (steam destroys structure)
8. Packaging: Sealed in sterile foil pouches

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Properties (IP Specifications)

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Mechanism of Haemostatic Action

1. Sponge placed on bleeding site → absorbs blood and tissue fluids
2. Physical matrix accelerates platelet aggregation and clot formation
3. Gelatin fibres provide scaffolding for fibrin deposition
4. Produces tamponade effect (mechanical compression)

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Applications

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Precautions:

• Do NOT use in contaminated wounds (promotes infection)
• Remove excess if possible — retained gelatin can support bacterial growth
• Do NOT use in CNS closure sites where there is CSF pressure
• Cannot be resterilized once opened
• Must remain dry until use

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Q4. Explain the types & characteristics & uses of Sutures & Ligatures including their advantages & disadvantages

Definitions

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Classification of Sutures

A. Based on Absorption

B. Based on Structure

C. Based on Origin

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Individual Suture Types

1. Surgical Catgut (Absorbable, Natural)

• Source: Submucosa of sheep intestine or serosa of beef intestine (collagen)
• Absorbed: By phagocytosis in 7–10 days (plain) or 20–40 days (chromic)
• Chromic catgut: Treated with chromium salts → slower absorption; less tissue reaction
• Uses: Ligature of small vessels, subcutaneous tissue, internal organs

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2. Silk (Non-absorbable, Natural)

• Source: Bombyx mori (silkworm) fibres; braided
• Tensile strength: High; remains in tissue for years (but becomes encapsulated)
• Uses: Skin closure, cardiovascular surgery, ophthalmic surgery

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3. Nylon (Polyamide) — Non-absorbable, Synthetic

• Strong, smooth, monofilament or braided
• Minimal tissue reaction
• Uses: Skin closure, fascia, microsurgery

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4. Polyglactin 910 (Vicryl) — Absorbable, Synthetic

• Copolymer of glycolide and lactide
• Absorbed by hydrolysis in 56–70 days (Vicryl); 42 days (Vicryl Rapide)
• Uses: Subcutaneous, deep tissue, GI anastomosis, pelvic surgery

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5. Polypropylene (Prolene) — Non-absorbable, Synthetic

• Extremely inert; does not degrade
• Monofilament; very smooth
• Uses: Cardiovascular surgery (permanent vascular anastomosis), hernia repair, skin

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6. Stainless Steel Wire — Non-absorbable, Metallic

• Maximum tensile strength
• Uses: Sternal (chest) closure after cardiac surgery, orthopaedic surgery, infected wounds

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Suture Sizes

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Evaluation / Quality Standards (IP)

• Tensile strength: Withstand defined breaking load per size
• Sterility: All sutures supplied sterile
• Knot pull strength: Must not slip
• Packaging: Individual sterile packets
• Needle attachment: Needle-suture junction must withstand 3× suture breaking load

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Q5. Discuss the formulation, properties & application of Medicated Bandages along with their role in Wound Management

Definition

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Types of Medicated Bandages

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Formulation of Zinc Paste Bandage (Unna's Boot) — Most Classic

• Zinc oxide — 15% w/w (astringent, antiseptic)
• Gelatin — 15% w/w (vehicle; sets on application)
• Glycerin — 40% w/w (plasticizer, humectant)
• Water — to 100% w/w

1. Dissolve gelatin in hot water with stirring (60–70°C)
2. Add glycerin; heat and stir to form smooth gel
3. Add zinc oxide (previously triturated smooth) into warm gelatin-glycerin base
4. Stir until uniform paste formed
5. Keep warm (40–50°C) during impregnation
6. Impregnate bandage fabric by machine or dipping into warm paste
7. Roll bandage; wrap in paper/foil
8. Allow to cool and set

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Properties of Medicated Bandages

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Role in Wound Management

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Advantages of Medicated Bandages

1. Local drug delivery — high local concentration at wound site
2. Sustained release — continuous release of medicament over hours
3. Simultaneous protection and treatment — wound covered while drug acts
4. Reduces dressing change frequency — stays in place 3–7 days
5. Reduces systemic side effects — minimal systemic absorption

Disadvantages:

1. Possible local irritation or contact dermatitis
2. Not suitable for highly exuding wounds (may macerate skin)
3. Drug stability issues in some bases
4. Limited to topical/local action only

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UNIT – X: INCOMPATIBILITIES IN PHARMACY

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Q1. Define Incompatibility & discuss their Types & Significance in Pharmaceutical Preparations

Definition

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Classification of Incompatibilities

INCOMPATIBILITIES
├── Physical Incompatibility
│   ├── Liquefaction (Eutectics)
│   ├── Immiscibility
│   ├── Precipitation
│   ├── Insolubility
│   └── Colour change (without chem. reaction)
├── Chemical Incompatibility
│   ├── Oxidation-Reduction
│   ├── Hydrolysis
│   ├── Double decomposition
│   ├── Polymerization
│   └── Gas evolution
└── Therapeutic Incompatibility
    ├── Synergism (overdose effect)
    ├── Antagonism (reduced efficacy)
    └── Side effects potentiation

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Significance of Incompatibilities

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Q2. Classify incompatibilities into Physical, Chemical & Therapeutic & explain each with suitable examples

A. PHYSICAL INCOMPATIBILITIES

Types:

1. Liquefaction / Eutectic Mixture

• Solid substances mix to form a liquid or soft mass at room temperature
• Examples:
  • Aspirin + Phenacetin
  • Camphor + Menthol → liquid
  • Thymol + Menthol → liquid

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2. Immiscibility

• Two liquids that do not mix (oil + water phases separate)
• Example: Cod liver oil + water without emulsifying agent

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3. Precipitation

• When two miscible liquids are mixed, one solute may come out of solution
• Example: Resinous tincture (e.g., Tincture Benzoin) added to aqueous solution → resin precipitates (water reduces alcohol content)
• Example: Spirit of Camphor + water → camphor precipitates

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4. Insolubility

• Drug prescribed in quantity exceeding its solubility in the vehicle
• Example: Iodine in water without potassium iodide

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5. Immiscibility of semisolids

• Mixing oily ointment base with water-based cream → separation
• Example: Wool fat ointment + aqueous cream → phase separation

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B. CHEMICAL INCOMPATIBILITIES

Types:

1. Oxidation-Reduction (Redox) Incompatibility

• Oxidizing agent + reducing agent react chemically
• Example: Potassium permanganate (KMnO₄) + Ferrous sulfate → KMnO₄ oxidizes Fe²⁺ to Fe³⁺; precipitation
• Example: KMnO₄ + glycerin → violent reaction / fire

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2. Double Decomposition (Precipitation Reactions)

• Exchange of ions forms insoluble precipitate
• Examples:
  • Calcium chloride + Sodium carbonate → CaCO₃ ↓ (white precipitate)
  • Lead acetate + Potassium iodide → PbI₂ ↓ (yellow precipitate)
  • Silver nitrate + Sodium chloride → AgCl ↓ (white precipitate)
  • Ferric chloride + Potassium iodide → precipitation

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3. Hydrolysis

• Drug hydrolyzes in the presence of water (especially acidic or alkaline)
• Example: Aspirin + water → acetic acid + salicylic acid (hydrolysis)
• Example: Atropine sulfate + alkali → inactive products
• Example: Penicillin in alkaline solution → destroyed

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4. Acid-Alkali Reactions

• Acids + alkaline drugs neutralize each other; salts may precipitate
• Example: Sodium bicarbonate + acidic drug (quinine sulfate) → quinine base precipitates
• Example: Tannic acid + alkaloid salts (quinine, strychnine) → insoluble alkaloidal tannates

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5. Complex Formation

• Drug + excipient forms complex → altered absorption or activity
• Example: Tetracycline + calcium → insoluble calcium tetracycline complex (chelation)
• Example: Tetracycline + iron → insoluble chelate

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6. Gas Evolution

• Reaction produces CO₂ or other gas
• Example: Sodium bicarbonate + citric acid → CO₂ (effervescent preparations — intended reaction; unintended in tablet coating)

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7. Colour Changes

• Indicate chemical reaction
• Example: Ferrous sulfate + tannic acid → dark blue-black ink (tannate formation)
• Example: Potassium iodide + starch → blue colour

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C. THERAPEUTIC INCOMPATIBILITIES

Types:

1. Pharmacodynamic Antagonism (Drug Antagonism)

• Two drugs with opposite pharmacological effects cancel each other
• Example: Morphine (CNS depressant) + Naloxone (opioid antagonist) → reversal of analgesia
• Example: Warfarin + Vitamin K → anticoagulant effect reduced
• Example: Beta-blocker + Salbutamol → bronchodilator effect reduced

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2. Pharmacodynamic Synergism / Potentiation (Overdose Effect)

• Two drugs with same action produce excessive effect
• Example: Alcohol + benzodiazepine → excessive CNS depression, respiratory arrest
• Example: Aminoglycoside + loop diuretic → additive ototoxicity
• Example: Two NSAIDs together → increased GI bleeding risk

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3. Pharmaceutical Antagonism

• Inactivation at the formulation level
• Example: Insulin + protamine → neutral protamine insulin (intended) but wrong ratio may cause altered duration

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4. Pharmacokinetic Interactions

• Drugs alter ADME of each other
• Absorption: Antacids reduce tetracycline absorption
• Distribution: Aspirin displaces warfarin from protein binding → increased anticoagulant effect
• Metabolism: Erythromycin inhibits CYP3A4 → increased cyclosporine levels
• Excretion: Probenecid blocks tubular secretion of penicillin → increased penicillin levels

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Q4. Discuss the methods to overcome Physical & Therapeutic Incompatibility with suitable examples

Methods to Overcome Physical Incompatibilities

1. Eutectic Mixtures (Liquefaction)

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2. Precipitation on Mixing Liquids

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3. Insolubility

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4. Immiscibility (Liquid-Liquid)

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Methods to Overcome Therapeutic Incompatibilities

1. Dose Adjustment

• Reduce dose of each drug when combination produces additive/synergistic toxicity
• Example: Use lower dose of each in CNS depressant combinations

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2. Separation in Time (Staggered Dosing)

• Administer interacting drugs at different times to minimize interaction
• Example: Tetracycline + antacids — take tetracycline 2 hours BEFORE antacid
• Example: Iron supplements + thyroxine — separate by 4 hours

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3. Route Change

• Administer one drug by a different route to avoid interaction
• Example: Give IV amikacin + oral gentamicin on different routes to reduce ototoxicity

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4. Drug Substitution

• Replace the interacting drug with a non-interacting alternative
• Example: Replace warfarin with heparin in a patient requiring aspirin
• Example: Replace tetracycline with azithromycin in patient on calcium supplements

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5. Antidotal Therapy (for toxic synergism)

• Use specific antidote to reverse toxic interaction
• Example: Opioid overdose (+ benzodiazepine) → Naloxone + Flumazenil

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6. Clinical Monitoring

• When interaction cannot be avoided — monitor carefully
• Example: Warfarin + aspirin → monitor INR closely; reduce warfarin dose

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7. Patient Counselling

• Educate patient about potential interactions and what to watch for
• Example: Patient on MAO inhibitor — counsel about avoiding tyramine-rich foods and sympathomimetics

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Q5. Explain the importance of identifying/detecting Incompatibilities in Prescription & Compounding Practice

Importance of Identifying Incompatibilities

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1. Patient Safety

• Formation of toxic substances — e.g., carbon monoxide or toxic salt formation
• Excessive pharmacological response — e.g., two CNS depressants together causing respiratory arrest
• Complete therapeutic failure — e.g., antibiotic inactivated by alkaline vehicle

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2. Legal & Professional Responsibility

• Under the Pharmacy Act and Drugs and Cosmetics Act, pharmacists are legally responsible for the quality and safety of compounded preparations
• Dispensing an incompatible prescription without correction or communication to the prescriber constitutes professional negligence
• Pharmacists must annotate or return incompatible prescriptions with explanation

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3. Role in Compounding Practice

• Read every component carefully
• Identify all active ingredients, vehicles, preservatives, excipients

• Check therapeutic incompatibilities (pharmacodynamic)
• Use drug interaction databases, BNF, IP appendices

• Are all ingredients soluble in the prescribed vehicle?
• Will any eutectic mixtures form?
• Will any precipitation occur on mixing?

• pH compatibility (most drugs stable at specific pH ranges)
• Oxidizing + reducing agents (must never be combined)
• Hydrolysis risk (aqueous solutions of hydrolysable drugs)

• Metal containers + tannic acid → black complex
• PVC IV bags + nitroglycerin → adsorption of drug to plastic
• Glass + strong alkali → silica leaching

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4. Importance in IV Admixture / TPN Preparation

• Precipitation in IV lines → emboli → pulmonary embolism
• Inactivation → therapeutic failure in critically ill patients
• Discolouration → signal of degradation

• Calcium gluconate + Phosphate in TPN → Calcium phosphate precipitation (can cause pulmonary emboli)
• Ceftriaxone + Calcium → precipitate in neonates (WHO warning)
• Amphotericin B with normal saline → precipitation (use 5% Dextrose only)

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5. Pharmacist Actions on Detecting Incompatibilities

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6. Documentation

• All detected incompatibilities must be documented in the dispensing record
• Prescriber must be informed whenever a prescription is modified
• Pharmacy management systems should have built-in interaction alerts

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7. Education & Awareness

• Pharmacists must stay updated with new drug interactions through:
  • Continuing education programs
  • BNF / Martindale updates
  • WHO drug alert bulletins
  • Clinical pharmacokinetics journals

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Sources: All answers are based on standard Pharmaceutics and Pharmacy Practice references — Cooper & Gunn's Dispensing for Pharmaceutical Students; Aulton's Pharmaceutics: The Design and Manufacture of Medicines; Remington's Pharmaceutical Sciences (21st Ed.); Indian Pharmacopoeia (2022); British Pharmacopoeia; Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems.