B Pharmacy Sem 1: Pharmaceutics I

Subject 3. Pharmaceutics I

1. 1. Introduction & Dosage Forms
   2. Pharmaceutical Calculations
   3. Powders & Granules
   4. Tablets
   5. Capsules
   6. Suppositories & Ophthalmic Preparations

Unit 1: Introduction & Dosage Forms

This unit explains the basics of pharmaceutics, what dosage forms are, why we use them, their types, how drugs are given into the body, and how to choose the right dosage form.

1.1 Pharmaceutics

Pharmaceutics is the area of pharmacy that deals with changing active drugs into medicines patients can safely and easily use. It involves studying the properties of drugs, choosing ingredients called excipients, designing dosage forms, and making sure medicines are stable, effective, and acceptable to patients. Pharmaceutics makes sure that when a patient takes a medicine, it works the right way and gives the desired therapeutic effect.

1.2 Dosage Forms

A dosage form is the physical way a medicine is prepared for use. It is a combination of the active drug and other safe substances to help deliver the drug properly. Examples include tablets, capsules, syrups, injections, creams, and eye drops. Dosage forms make drugs easier to take, protect them from damage, control how fast they are released, and target specific parts of the body.

1.3 Need for Dosage Forms

Dosage forms are needed to:

• Accurately measure and give the correct dose

• Protect drugs from air, light, moisture, or stomach acid

• Make drugs taste or smell better for patients

• Allow the drug to act locally or systemically as required

• Control how fast or slow the drug is released in the body

• Help patients take medicine easily and correctly

1.4 Classification by Physical State

Dosage forms can be classified into:

• Solid forms: tablets, capsules, powders, granules. These are stable, easy to handle, and give precise doses.

• Liquid forms: syrups, suspensions, emulsions, solutions. These are useful for children, elderly, or people who cannot swallow solids.

• Semisolid forms: creams, ointments, gels, pastes. These are used on skin, eyes, or mucous membranes.

• Gaseous forms: inhalers, aerosols. These deliver drugs directly to the lungs for fast action.

1.5 Classification by Route of Administration

Dosage forms can also be classified by how they are given:

• Oral: taken by mouth (tablets, capsules, syrups)

• Parenteral: given by injection (intravenous, intramuscular, subcutaneous)

• Topical: applied on skin or eyes (creams, ointments, eye drops)

• Inhalation: breathed in through mouth or nose (inhalers, nebulizers)

• Rectal: inserted into rectum (suppositories)

• Vaginal: inserted into vagina (pessaries, vaginal tablets)

• Sublingual or buccal: placed under the tongue or in the cheek (quick absorption, e.g., nitroglycerin tablets)

• Transdermal: applied as patches on the skin for slow, continuous drug release

• Nasal: sprayed or dropped into the nose (nasal sprays)

1.6 Routes of Administration

• Oral route is the most common, easy, and convenient, but absorption can be slow and affected by food or stomach acid.

• Parenteral route gives fast action and is used in emergencies but needs sterile injections and trained people to administer.

• Topical route is used for local action on skin or eyes, giving fewer side effects.

• Inhalation route delivers drugs quickly to the lungs, used in asthma or COPD.

• Rectal or vaginal routes are helpful when the patient cannot take oral medicines due to vomiting or unconsciousness.

• Sublingual or buccal routes give very fast action, useful for emergencies like chest pain.

• Transdermal route gives slow and steady drug release over hours or days.

• Nasal route gives quick absorption through nasal mucosa.

1.7 Advantages of Dosage Forms

• Protect drugs from air, light, moisture, or stomach acid

• Improve taste, smell, and appearance of medicines

• Provide accurate and easy dosing

• Allow drugs to be delivered exactly where needed

• Make it easier for patients to take medicines regularly

• Control release of drugs for immediate, delayed, or sustained effects

1.8 Disadvantages of Dosage Forms

• Some dosage forms are complex and costly to produce

• Liquids and some semisolids can spoil faster and may need preservatives

• Injections can be painful and require trained personnel

• Some routes like rectal or vaginal may be uncomfortable or unacceptable to some patients

• Absorption of drugs can vary due to body factors (e.g., rectal contents, skin condition)

1.9 Factors Affecting Choice of Dosage Form

When choosing the right dosage form, factors include:

• Physicochemical properties of the drug: solubility, stability, pH, taste, and melting point

• Patient factors: age, ability to swallow, allergies, mental status, preferences

• Desired speed of action and how long the drug effect should last

• Target organ or site where the drug needs to act

• Manufacturing feasibility, cost, packaging, and storage requirements

• Legal and regulatory guidelines to ensure patient safety and product quality

1.10 Key Points for Exams

• Know what pharmaceutics and dosage forms are

• Be able to list solid, liquid, semisolid, and gaseous dosage forms

• Learn routes of administration with examples of dosage forms used in each route

• Remember why dosage forms are needed and what advantages they provide

• Understand factors that decide which dosage form is best for a drug and a patient

Unit 2: Pharmaceutical Calculations

This unit teaches the mathematical methods needed to prepare and prescribe medicines accurately. You’ll learn systems of weights and measures, how to express drug strengths, perform dilutions and alligation, calculate doses for patients, and determine rates of infusion.

2.1 Systems of Weights and Measures

British (Avoirdupois) System

• Uses pounds (lb), ounces (oz), drams (dr) and grains (gr)

• 1 lb = 16 oz; 1 oz = 437.5 gr
  Metric System

• Uses kilograms (kg), grams (g), milligrams (mg), micrograms (µg), and liters (L)

• 1 kg = 1000 g; 1 g = 1000 mg; 1 mg = 1000 µg

2.2 Percentage Strengths

Weight-in-Volume (% w/v)

• Grams of drug per 100 mL of solution (e.g., 5 g in 100 mL = 5% w/v)
  Weight-in-Weight (% w/w)

• Grams of drug per 100 g of preparation (e.g., 2 g in 100 g = 2% w/w)
  Volume-in-Volume (% v/v)

• mL of solute per 100 mL of solution (e.g., 10 mL in 100 mL = 10% v/v)

2.3 Ratio Strengths

• Expressed as “1 part in X parts” (e.g., 1 : 100 means 1 g in 100 g or mL)

• Useful for tinctures, ointments, and dilutions where percentage is less convenient

2.4 Alligation

Alligation Alternate

• Method for mixing two strengths to achieve a desired percentage

• Calculate parts of each concentration using the “difference” rule plotted on a grid
  Alligation Medial

• To find mean concentration when mixing known weights/volumes

2.5 Dilution and Concentration

• C₁V₁ = C₂V₂: The concentration–volume equation for making dilutions

  • C₁ = initial concentration, V₁ = volume of stock solution

  • C₂ = desired concentration, V₂ = final total volume

• Used to prepare injections, ophthalmic solutions, and oral liquids

2.6 Dosage Calculations

Dose Based on Body Weight

• Dose (mg) = Recommended dose (mg/kg) × Patient’s weight (kg)
  Body Surface Area (BSA) Method

• BSA (m²) = √[(height (cm) × weight (kg)) / 3600]

• Dose = Dose per m² × BSA
  Intravenous Infusion Rates

• Rate (mL/hr) = Total volume (mL) / Time (hr)

• Drops per minute = (Total volume × Drop factor) / (Time in minutes)

2.7 Acid–Base and Osmotic Equations

Henderson–Hasselbalch Equation

• pH = pKa + log([A⁻] / [HA]) for buffer preparations
  Osmolarity Calculations

• mOsmol/L = (Weight of solute (g/L) / Molar mass) × Number of particles × 1000

2.8 Worked Examples

1. Preparing 250 mL of 2% w/v solution

   • 2 g in 100 mL → for 250 mL, amount = (2 g/100 mL) × 250 mL = 5 g

2. Diluting 10% to 1%

   • C₁V₁ = C₂V₂ → 10% × V₁ = 1% × 100 mL → V₁ = 10 mL stock + 90 mL diluent

3. Alligation to get 3% from 1% and 5%

   • Difference: |5–3| = 2 parts 1%, |3–1| = 2 parts 5% → mix equal volumes

2.9 Key Points for Exams

• Memorize unit conversions between systems of weights and measures

• Practice writing strengths in % w/v, w/w, v/v, and ratio form

• Master C₁V₁ = C₂V₂ for all dilutions

• Be comfortable with alligation method for mixing concentrations

• Know formulas for dose by weight and BSA, and for IV infusion rates

• Understand when to use Henderson–Hasselbalch and osmolarity calculations

3.1 Overview of Powders & Granules

Fine particles of drug (powders) or aggregated particles (granules) designed for oral, topical, or inhalation use. Powders mix easily with liquids, granules improve flow and compressibility for tableting or encapsulating.

3.2 Classification of Powders & Granules

3.3 Why Powders & Granules Are Used

• Allow flexible dosing for children or elderly

• Mix easily into suspensions or solutions

• Rapid drug release and absorption

• Improved stability compared to liquids

• Granules flow and compress well for tablets/capsules

3.4 Limitations

• Dust generation can irritate respiratory tract

• Uniform mixing challenging for potent drugs

• Hygroscopic powders may cake on storage

• Inhalation powders require precise particle size control

3.5 Common Excipients

• Diluent/Fillers: Lactose, starch

• Glidants: Colloidal silica, talc (improve flow)

• Lubricants: Magnesium stearate (prevent sticking)

• Disintegrants: Cross‑linked PVP, starch (aid breakup in fluid)

• Binders (for granules): PVP, methylcellulose

3.6 Preparation Methods

For Powders

1. Trituration: Grinding drug with mortar and pestle to reduce size

2. Levigation: Incorporating small amount of liquid to wet and grind sticky powders

3. Sifting: Passing mixture through a mesh to break up aggregates

4. Milling: Mechanical comminution for large‑scale particle reduction

For Granules

1. Wet Granulation

   • Mix powders with binder solution

   • Pass wet mass through sieve to form granules

   • Dry and sieve to uniform size

2. Dry Granulation

   • Compress powder blend into large sheets or slugs

   • Mill into granules without using liquid

3. Slugging and Roller Compaction

   • Form slugs under pressure, then break down into granules

3.7 Evaluation Tests

• Flow Properties: Angle of repose, Carr’s index, Hausner ratio

• Particle Size Distribution: Sieve analysis, laser diffraction

• Bulk & Tapped Density: For packing and flow

• Moisture Content: Loss on drying or Karl Fischer titration

• Assay & Uniformity: Ensure correct drug content in each dose

• Disintegration & Dissolution (for granules/tablets): Release profile

3.8 Packaging & Storage

• Store in tight, moisture‑proof containers (desiccants if needed)

• Protect light‑sensitive powders in amber bottles

• Label with “Use within” date after opening

• Avoid high humidity and extreme temperatures

3.9 Key Points for Exams

• Be able to list and describe bulk vs. divided powders and types of granules

• Memorize preparation steps for trituration, sifting, wet and dry granulation

• Know why granules flow better and how that aids tableting

• Understand evaluation tests (angle of repose, Carr’s index, moisture content)

• Recall packaging needs to protect from moisture, light, and air

Unit 4: Tablets

This unit covers tablets, the most common solid dosage form. You’ll learn what tablets are, why they’re used, types of tablets, key excipients, manufacturing methods, evaluation tests, and storage considerations.

4.1 Tablets

Tablets are solid doses of medicine formed by compressing drug with excipients. They offer precise dosing, ease of handling, and can be designed for immediate or controlled release.

4.2 Types of Tablets

4.3 Excipients in Tablets

• Diluent/Fillers: Lactose, microcrystalline cellulose – provide bulk

• Binders: PVP, starch paste – hold granules together

• Disintegrants: Cross‑linked PVP, sodium starch glycolate – help tablet break apart

• Lubricants: Magnesium stearate, stearic acid – prevent sticking to punches

• Glidants: Colloidal silica, talc – improve powder flow

• Coating Materials: Shellac, cellulose derivatives – mask taste and control release

4.4 Manufacturing Methods

4.4.1 Direct Compression

• Mix drug and excipients that flow and compress well

• Compress directly into tablets

• Fast and cost‑effective; needs good excipient properties

4.4.2 Wet Granulation

1. Mix drug with dry excipients

2. Add binder solution to form wet mass

3. Pass through sieve to make granules

4. Dry granules, mill, add lubricants, and compress

• Improves flow and uniformity; most common method

4.4.3 Dry Granulation

• Compress powder blend into large slugs or sheets

• Mill to form granules

• No heat or solvents; suitable for moisture‑ or heat‑sensitive drugs

4.4.4 Tablet Coating

• Sugar Coating: Sweet, glossy finish; multiple steps, thick layer

• Film Coating: Thin polymer film; faster, less bulky than sugar

• Enteric Coating: Acid‑resistant polymers to protect drug from stomach

4.5 Evaluation of Tablets

• Appearance: Uniform shape, color, and free from cracks

• Weight Variation: Ensure each tablet is within ± 5% of average weight

• Hardness (Crushing Strength): Tablet can withstand pressure during handling

• Friability: Tablets should not crumble (< 1% weight loss in friabilator)

• Disintegration Time: Time to break into particles in specified fluid

• Dissolution Test: Rate and extent of drug released in medium

• Content Uniformity: Each tablet contains correct amount of drug

4.6 Packaging & Storage

• Pack in blister packs or tightly closed bottles to protect from moisture and air

• Store at controlled room temperature (15–25 °C) unless specified

• Label with “use by” date after opening to ensure potency

4.7 Key Points for Exams

• Know the main types of tablets and their applications

• Remember core excipients and their functions

• Understand differences between direct compression, wet, and dry granulation

• Be able to list and describe evaluation tests (hardness, friability, disintegration, dissolution)

• Recall basic coating types and why coatings are used

Unit 5: Capsules

This unit explains capsules as a solid dosage form, covering their design, types, formulation components, manufacturing methods, evaluation tests, packaging, and exam–critical points.

5.1 What Capsules Are

Capsules consist of a drug-filled shell made from gelatin or plant‑based polymers. They enclose powders, granules, pellets, or liquids, masking taste and odor and allowing easy swallowing or controlled release.

5.2 Types of Capsules

5.3 Key Ingredients

• Shell Material

  • Gelatin: Derived from animal collagen; widely used.

  • HPMC (Hydroxypropyl Methylcellulose): Vegan alternative; stable.

• Fill Materials

  • Diluent/Fillers: Lactose, microcrystalline cellulose – add bulk.

  • Glidants: Colloidal silica – improve flow into shells.

  • Disintegrants: Cross‑linked PVP – help fill break apart.

  • Binders: PVP solution – agglomerate powders for granules.

  • Lubricants: Magnesium stearate – ensure smooth filling.

5.4 Manufacturing Methods

5.4.1 Hard Capsule Filling

1. Sort and check empty shells for defects.

2. Prepare dry powder or granules blend.

3. Orient and lock capsule bodies in filling machine.

4. Fill powder into bodies, replace caps, and eject filled capsules.

5. Clean off excess powder and inspect.

5.4.2 Soft Capsule Formation

1. Prepare liquid or paste fill.

2. Form continuous gelatin ribbon.

3. Enclose fill between two ribbons in rotary dies.

4. Seal edges by heat and cutting into individual capsules.

5. Dry, polish, and inspect.

5.4.3 Special Coating (if required)

• Spray enteric‐coating solution onto filled capsules.

• Dry and cure coating to ensure acid resistance.

5.5 Evaluation Tests

• Weight Variation: Check each capsule’s total mass variation (< ± 5%).

• Disintegration Test: Time for shell to open and release fill in fluid.

• Dissolution Test: Rate and amount of drug released into solution.

• Moisture Content: Ensure shells are neither too brittle nor too soft.

• Leakage Test (softcaps): Check for fill loss under pressure.

• Content Uniformity: Each capsule has correct drug amount.

5.6 Packaging & Storage

• Hard Capsules: Pack in blister packs or bottles with desiccant to control moisture.

• Soft Capsules: Use tight‑seal bottles or pouches; avoid high heat to prevent shell softening or fusion.

• Label with storage conditions (e.g., 15–25 °C) and “Use by” date.

5.7 Key Points for Exams

• Know the differences between hard and soft shells.

• Remember common shell materials (gelatin vs. HPMC).

• Be able to outline the filling steps for hard and soft capsules.

• List major evaluation tests and why moisture control is vital.

• Understand why modified‑release and enteric capsules are used.

Unit 6: Suppositories & Ophthalmic Preparations
This unit covers two special dosage forms—suppositories, which are inserted into body orifices, and ophthalmic preparations, which are instilled in the eye. Both require unique bases, strict sterility or cleanliness, and careful manufacturing to ensure safety and effectiveness.

6.1 Suppositories

What a Suppository Is
A suppository is a solid, conical, or torpedo‑shaped dose designed for insertion into the rectum, vagina, or urethra. It melts, softens, or dissolves at body temperature, releasing drug locally or systemically.

Types of Suppositories

Why Use Suppositories

• Bypass first‑pass metabolism: Increases bioavailability of certain drugs.

• Alternative for GI issues: Useful when patients vomit, are unconscious, or can’t swallow.

• Local or systemic action: Treat hemorrhoids locally or provide systemic analgesia.

• Minimize stomach irritation: Avoids gastric mucosal damage.

Limitations

• Patient discomfort: Insertion may be embarrassing or painful.

• Variable absorption: Dependent on rectal contents and regional blood flow.

• Risk of expulsion: Movement or bowel activity can expel the dose prematurely.

Suppository Bases

• Fatty (Oleaginous) Bases

  • Cocoa butter (Theobroma oil): Melts sharply at 34–36 °C for predictable release.

  • Synthetic fats (e.g., Witepsol, Fattibase): Offer uniform melting points and better stability.

• Water‑Soluble/Semisynthetic Bases

  • Glycerinated gelatin: Dissolves slowly, hygroscopic—best for vaginal use.

  • Polyethylene glycols (PEG): Dissolve in body fluids; no melting, suitable for heat‑sensitive drugs.

Formulation Considerations

• Displacement Value: Weight of base displaced by unit weight of drug—ensures correct dose.

• Lubricants: e.g., liquid paraffin to ease removal from molds.

• Surfactants/Emulsifiers: Improve wetting and release (e.g., Tween 80).

• Preservatives: Necessary with high water content bases to prevent microbial growth.

Manufacturing Methods

1. Fusion Molding (most common)

   • Melt base → Incorporate drug uniformly → Pour into pre‑lubricated molds → Cool and eject.

2. Compression Molding

   • Mix drug with base in powdered form → Compress into shape under high pressure → No heat exposure.

3. Hand Rolling & Shaping

   • Traditional for small batches: Knead base‑drug mixture, roll into cylinders, cut to size, shape ends by hand.

Quality Control Tests

• Appearance & Surface: Smooth, free of cracks or blemishes.

• Weight Variation: Each within ± 5% of the mean.

• Melting Range or Softening Time: Matches physiological conditions.

• Disintegration Time: Completes within specified limits in simulated fluids.

• Content Uniformity: Each contains correct drug amount by assay.

• Liquefaction Time: Time to fully liquefy at 37 °C.

6.2 Ophthalmic Preparations

What Ophthalmics Are
Sterile products intended for administration to the eye. They include solutions (drops), suspensions, ointments, lotions, and inserts, each designed to deliver drug safely without irritation or infection.

Ideal Characteristics

• Sterile & Pyrogen‑Free: No microbes or fever‑causing toxins.

• Particle‑Free (Solutions): Avoid corneal abrasion or irritation.

• Isotonic (≈0.9% NaCl): Matches tear fluid to prevent discomfort.

• pH 7.0–7.4: Close to tear pH for comfort and drug stability.

• Viscosity: Slightly thickened for better retention but not so thick as to blur vision.

• Preservatives (if multi‑dose): e.g., benzalkonium chloride; avoid when corneal injury is present.

Types & Examples

Formulation Components

• Solvents: Water for injection; may include co‑solvents like glycerin.

• Tonicity Agents: NaCl or dextrose to adjust osmolarity.

• Buffers: Borate or phosphate salts to maintain pH.

• Viscosity Enhancers: Cellulose derivatives (HPMC, CMC) to slow drainage.

• Preservatives: Only when multi‑dose; choice depends on compatibility and patient safety.

Manufacturing Precautions

• Aseptic Processing: Conducted in laminar‑flow hoods under sterile conditions.

• Sterile Filtration: 0.22 µm filters remove microbes from solutions.

• Closed Filling Systems: Minimize exposure to air and contaminants.

Evaluation Tests

• Sterility Tests: Culture‑based or rapid methods to confirm absence of microbes.

• Clarity & Particulate Matter: Visual inspection and light obscuration tests.

• pH Measurement: Must remain within specified range.

• Osmolarity/Tonicity: Checked with osmometer or freezing‑point depression.

• Viscosity: Measured to ensure proper drop formation and retention.

• Drug Content & Uniformity: Each batch meets potency specifications.

Key Points for Exams

• Know routes, shapes, and uses of rectal, vaginal, and urethral suppositories.

• Understand fatty versus water‑soluble bases and why each is chosen.

• Be able to describe displacement value, molding methods, and key QC tests for suppositories.

• Recall sterile technique, ideal properties, and formulation ingredients for eye drops, ointments, and inserts.

• List critical evaluation tests and storage requirements to maintain safety and efficacy.

Pharmaceutics I: Quick Overview

1. Introduction & Dosage Forms
   Explores how pure drugs become patient‑ready medicines. Covers what dosage forms are, why we need them, how they’re classified by physical state (solid, liquid, semisolid, gas) and by route (oral, injectable, topical, inhaled, etc.), and key factors in choosing the right form.

2. Pharmaceutical Calculations
   Teaches weight/volume systems (metric and imperial), expressing strengths (% w/v, w/w, v/v, ratios), dilution formulas (C₁V₁=C₂V₂), alligation methods, dose calculations (mg/kg, BSA), and IV infusion rates.

3. Powders & Granules
   Details fine particles (powders) and aggregated particles (granules): their uses, advantages (flexible dosing, rapid release), common excipients, preparation (trituration, granulation), evaluation (flow, particle size, moisture), and storage.

4. Tablets
   Covers types (immediate, chewable, effervescent, sustained‑release, enteric‑coated, orally disintegrating), core excipients (diluents, binders, disintegrants, lubricants, glidants), manufacturing (direct compression, wet/dry granulation, coating), and QC tests (hardness, friability, disintegration, dissolution).

5. Capsules
   Explains hard and soft gelatin (or HPMC) shells filled with powders, granules, or liquids; modified‑release and enteric variants; key ingredients; filling methods; and evaluation (weight variation, disintegration, dissolution, moisture control).

6. Suppositories & Ophthalmic Preparations
   Describes suppositories (rectal, vaginal, urethral) with fatty or water‑soluble bases, molding methods, displacement values, and QC tests. Covers sterile eye products (drops, suspensions, ointments, inserts): ideal properties (sterility, isotonicity, pH), excipients, aseptic manufacturing, and evaluation (sterility, clarity, viscosity, tonicity).