Pharmaceutics I — Study Notes by Source Summary & Study Notes

6 Powders & Granules-1.pptx 📄

• What this source covers:
  • Basic definitions and uses of powders, granules, and effervescent granulated salts.
  • How particle size and particle properties affect formulation and processing (micromeritics).
  • Measurements (true volume, void, porosity, densities), comminution and blending techniques, types of powders, and granule preparation.

Fundamental building blocks (start very small)

• A solid drug can be broken into many tiny pieces called particles; a collection of these particles in dry form is a powder.
  • powder: a dry substance made of finely divided solid particles used internally or externally.
• A granule is a larger, often compacted agglomerate of powder particles used to improve flow and stability.
  • granule: particles larger than typical powder fines (commonly 4–12 mesh).

Why particle size and shape matter (intuitive layer)

• If particles are similar in size they mix more evenly; different sizes cause segregation (fines sink or rise depending on mixing).
• Particle size influences:
  • Dissolution rate (smaller → larger surface area → faster dissolution).
  • Feel in the mouth (grittiness), suspendability, and uniformity when mixed in liquids.
• Particle shape (spherical vs. needle) affects packing and flow.

Measuring particle size (practical methods)

• Visual/Imaging:
  • Optical microscopy for particles > ~1 µm.
  • SEM (scanning electron microscopy) for surface morphology and smaller particles.
  • TEM (transmission electron microscopy) for nanoparticles.
• Sieving: passing powder through progressively finer meshes gives USP descriptive grades (e.g., #8, #20, #40, #60, #80).
• Other techniques: sedimentation rate, dynamic light scattering (DLS), cascade impaction (for aerosols), laser holography.

USP descriptive particle size terms (simple mapping)

• Very Coarse = #8 sieve ≈ 2,360 µm; Coarse = #20 ≈ 850 µm; Moderately Coarse = #40 ≈ 425 µm; Fine = #60 ≈ 250 µm; Very Fine = #80 ≈ 180 µm.

Micromeritics — the science of small particles (core concepts)

• Start with volumes:
  1. True volume = space occupied by the solid material of particles alone (no pores).
  2. Bulk volume = macroscopic volume taken by the powder including the spaces between particles.
  3. Void (void volume) = bulk volume − true volume (the empty space between particles).
• Porosity (ɛ) measures how much of the bulk volume is void: Porosity = Void / Bulk volume; often shown as a percent (Porosity × 100%).
• Densities:
  • True density: mass / true volume; density of the particle material itself.
  • Apparent (bulk) density: mass / bulk volume; how dense the powder pack appears.
  • Tapped density: apparent density after tapping/compaction; used to assess compressibility.
• Bulkiness (B) is the reciprocal of apparent density: B = 1 / Pa (units: mL/g). Use bulkiness to choose container size.

Angle of repose and flowability (idea first)

• Imagine pouring sand through a funnel — the slope the pile makes tells you how well it flows.
  • Low angle of repose → powder flows freely; high angle → poor flow.
• Flowability also depends on electrostatic charge and humidity.

Important particle behaviors related to moisture (explain then name)

• If a substance picks up moisture but does not dissolve, it becomes sticky — this is called hygroscopic.
• If it absorbs moisture and liquefies (forms solution), it is deliquescent.
• If a crystalline powder contains water of crystallization and releases it on handling, becoming sticky, it is called efflorescent.
• Practical control: store dry, use desiccants, or add inert drying powders.

Compressibility, compactibility, and flowability (clear definitions)

• Compressibility: how much a powder reduces in volume under pressure.
• Compactibility: how well a powder forms a coherent tablet on compression.
• Flowability: how well a powder moves without sticking; critical for capsule/tablet filling.

Comminution — reducing particle size (methods & why)

• Purpose: increases dissolution, aids extraction, improves mixing.
• Manual methods (definitions after idea):
  • trituration: rubbing or grinding materials together to reduce size and/or mix them.
  • levigation: grinding a powder with a small amount of liquid (insoluble in powder) to reduce grittiness.
  • spatulation: mixing small quantities using a spatula on a slab; useful for sensitive/eutectic mixtures.

Blending powders (goal then techniques)

• Goal: homogeneous mix of all components.
• Techniques (from smallest-scale to industrial):
  1. Geometric dilution — start with a small amount of potent drug and dilute stepwise with equal portions of diluent.
  2. Trituration — mixing with grinding.
  3. Spatulation — light mixing for small batches.
  4. Sifting — passes powder through sieve to lighten and mix.
  5. Tumbling (blenders) — common in industry (e.g., twin-shell blenders).

Special issue: eutectic mixtures (explain then manage)

• When two solids mix and melt at a lower temperature than either alone, they form a eutectic — can become pasty or liquid on mixing.
• Ways to avoid problems:
  • Dispense components separately.
  • Add an absorbent (talc, starch, lactose) to incorporate the liquid.
  • Keep incompatible ingredients physically separated.

Types of medicated powders (simple categories)

• Bulk powders: patient measures the dose (must be easy to use; typically pass a #100 mesh sieve for fineness).
• Divided powders (chartulae): single-dose packets for potent drugs; reduce patient dosing error.
• Dusting powders: topical blends that should spread and cling without irritating skin.
• Aerosol powders and insufflations: intended for inhalation or body cavities — require specific particle size (1–6 µm for lung deposition).

Granules (what and how)

• Granules are larger agglomerates made to improve flow, reduce dust, and improve stability (especially for hygroscopic or unstable drugs).
• Preparation methods:
  • Wet granulation: moisten blended powders, pass through screen, dry, and optionally spray flavors.
  • Dry granulation (roll compaction): compress powder into sheets then mill to granules.

Effervescent granules (concept then use)

• Combine an acid (citric/tartaric) with bicarbonate so that when dissolved in water they effervesce (release CO2), masking taste and producing a pleasant vehicle.
• Dispense in moisture-protective containers (packets or wide-mouth bottles) and instruct patient to dissolve in water before ingestion.

Worked example (Group Exercise) — solve step-by-step

Problem: Magnesium carbonate has a true density of 3.0 g/cc. Experimentally you find 3.5 g of the powder measures 50 mL. Find: True Volume, Void, Porosity, Apparent Density (P_a), Bulkiness.

Solution:

1. True volume = mass / true density = 3.5 g ÷ 3.0 g/mL = 1.1667 mL.
2. Bulk volume (given) = 50 mL.
3. Void = Bulk volume − True volume = 50 − 1.1667 = 48.8333 mL.
4. Porosity = Void / Bulk volume = 48.8333 ÷ 50 = 0.976666 → 97.67%.
5. Apparent density P_a = mass / Bulk volume = 3.5 g ÷ 50 mL = 0.07 g/mL.
6. Bulkiness B = 1 / P_a = 1 ÷ 0.07 = 14.2857 mL/g.

Practical takeaways (quick rules)

• Light powders: large gaps, low apparent density, large bulk volume.

• Heavy powders: small gaps, high apparent density, small bulk volume.

• For tablets/capsules: apparent density affects tablet hardness and disintegration time.

• Control moisture-sensitive powders with drying agents or by converting to granules.

• Key terms to remember: powder, granule, hygroscopic, porosity, apparent density.

7 Capsules & Tablets.pptx 💊

• What this source covers:
  • Definitions, pros/cons, and formulation components of hard and soft gelatin capsules.
  • Types of tablets, excipients used, coating types, and compendial quality tests (disintegration, dissolution, uniformity).

Start from the simplest idea: what is an oral solid dosage form?

• A single unit you swallow that contains a measured amount of drug; common forms are capsules and tablets.
• They deliver a specific dose reliably, are convenient to store/transport, and often cost-effective.

Capsules — the shell idea first

• Purpose: enclose the drug inside an edible shell to make dosing easy and mask taste.
• Two main types:
  • Hard gelatin capsules: two-piece shells filled with powders/granules; gelatin plus plasticizers (small % water) in shell.
  • Soft gelatin capsules: one-piece, hermetically sealed shells that encapsulate liquids, suspensions, or pastes; shells contain gelatin + plasticizers (e.g., glycerin, sorbitol).

Why use capsules? (advantages then limits)

• Advantages: easy to swallow, pleasant appearance (colors/imprints), flexible dosing, minimal measuring devices required, faster onset than some tablets (if no disintegration needed).
• Disadvantages: moisture sensitivity (shells can dry or swell), not ideal for drugs degraded in GI, stability concerns with hygroscopic contents, and potential for patient ‘‘burp-back’’ for some oils.

Capsule shell components & handling

• Shell ingredients: gelatin, water (plasticizer level ~13–16%), coloring agents (FD&C and D&C dyes or lake pigments), and opacifiers (titanium dioxide).
• Color agents: dyes (soluble) versus lake pigments (insoluble, less migration).
• Protection: add desiccants to packaging to control moisture.

Capsule formulation steps (high level)

1. Comminute or size-reduce ingredients as needed.
2. Blend thoroughly to ensure dose uniformity.
3. Add diluents/adsorbents if needed to make fills manageable.
4. Fill the shells (manually for extemporaneous or by automated machines for manufacturing).
5. Close/seal and perform quality control (weight variation, content uniformity).

Capsule excipients (short list with purpose)

• Diluents (fillers): add bulk (lactose, cellulose).
• Glidants: improve flow (colloidal silica, talc).
• Disintegrants: help contents disperse on ingestion (pre-gelatinized starch).
• Wetting agents/surfactants: improve dissolution of hydrophobic drugs.
• Lubricants: ease processing (magnesium stearate usually used more in tablets).

Special capsule techniques

• Capsule within a capsule or tablet within capsule for potent drugs or incompatible combinations.
• Soft gels are used for oils or poorly soluble liquids.
• Sealing methods: hydroalcoholic seal, heat pin, gelatin band, or gelatin sealing for high-throughput machines.

Compendial tests important to capsules (explain then name)

• Disintegration test: measures time for capsule to break up into a soft mass—does not mean complete dissolution.
• Dissolution test: measures rate and extent of drug release into a specified medium using USP apparatuses.
• Content uniformity/weight variation: ensure each unit contains close to labeled amount (criteria typically 85–115% for most units).
• Packaging requirements: tight, well-closed, light-resistant if needed.

Tablets — basic concept then variety

• A tablet compresses drug + excipients into a solid dose. Most are made by compression but some are molded.
• Types (with quick explanation):
  • Compressed tablets (single-compression)
  • Multiple or layered tablets (more than one compression)
  • Sugar-coated (large coating, masks taste)
  • Film-coated (thin polymer coating, efficient)
  • Enteric-coated (dissolve at higher pH to avoid stomach)
  • Buccal and sublingual (dissolve in mouth for local/rapid systemic absorption)
  • Chewable (for those who cannot swallow; often mannitol used)
  • Effervescent tablets (release CO2 in water)
  • Rapidly disintegrating/dissolving tablets (for quick onset and ease of swallowing)
  • Extended-release tablets (control rate of drug release to reduce dosing frequency)

Tablet excipients (why each is used)

• Diluents: add bulk and assist compression (lactose, microcrystalline cellulose).
• Binders/adhesives: hold particles together (PVP, cellulose derivatives).
• Disintegrants: cause tablet to break apart in GI (starch, croscarmellose).
• Lubricants: reduce friction during ejection (magnesium stearate).
• Glidants: improve powder flow into dies (colloidal silica).
• Antiadhesives: prevent sticking to tablet punches.

Coating types (what they do and how)

• Sugar coating: many layers of syrup; masks taste but adds bulk and time.
• Film coating: thin polymer layer; protects from abrasion and can control appearance with less bulk.
• Gelatin coating (glencap/GELCAP): thin gelatin layer to ease swallowing.
• Enteric coatings: polymers that dissolve at pH ≳ 4.8 so drug is released in intestine.

Special tablets and routes

• Buccal/sublingual tablets dissolve in the mouth to allow absorption through mucosa, bypassing stomach acidity.
• Vaginal inserts/rectal tablets (inserts) are compressed tablets intended for insertion rather than swallowing.

Quality & compendial requirements for tablets (quick list)

• Thickness, hardness, friability (tendency to crumble; acceptable loss ~1%), disintegration time, dissolution profiles, content uniformity, and imprinting for identification.
• Imprinting: required for marketed human dosage forms to ensure product identification.

Practical formulation considerations (short checklist)

• Evaluate drug-excipient compatibility and hygroscopicity.

• Decide on immediate vs. modified release based on drug properties.

• Choose excipients to ensure flow, compressibility, taste masking, and stability.

• Run compendial tests during development and before release.

• Key terms to memorize: capsule, tablet, disintegration, dissolution.

8 Ointments Creams Gels.pptx 🧴

• What this (typical) source would cover:
  • Definitions and basic differences among ointments, creams, and gels.
  • Bases, preparation methods, absorption, and selection criteria for topical semisolids.

Start with the simplest distinction: what is a topical semisolid?

• Topical semisolids are dosage forms applied to the skin or mucous membranes to deliver drug locally (or sometimes systemically).
• The main categories are:
  • ointment: typically a semisolid, oily, and occlusive preparation that stays on the skin and prevents moisture loss.
  • cream: an emulsion (oil-in-water or water-in-oil) that is less greasy and easier to wash off than ointments.
  • gel: a semisolid system where a liquid phase is constrained in a three-dimensional network (non-greasy, often water-based).

What makes them different (layering of ideas)

• Base type controls feel, occlusivity, and drug release:
  • Ointment bases (oleaginous) are greasy and form an occlusive film; good for very dry skin or when prolonged contact is needed.
  • Creams (emulsions) are more cosmetically acceptable and easier to apply and remove; good for normal to slightly dry skin.
  • Gels are cooling, non-greasy, and suitable for hairy areas or where a quick-drying formulation is desired.
• Selection depends on desired residence time, drug solubility (lipophilic drugs favor ointments), and patient preference.

Common bases and their properties (simple list)

• Oleaginous (hydrocarbon) bases: petrolatum — highly occlusive, non-washable, good for lipophilic drugs.
• Absorption bases: can take up water and form w/o emulsions; useful when some water is needed in formulation.
• Water-removable bases: creams (o/w emulsions) — washable and less occlusive.
• Water-soluble bases: polyethylene glycol (PEG) ointments — non-greasy and can dissolve both hydrophilic and some lipophilic drugs depending on partitioning.

How drugs are released from semisolids (simple mechanism)

• Drug must partition from the base into the skin surface; partition coefficient and solubility determine rate.
• Occlusion increases hydration of stratum corneum and generally increases drug penetration.

Preparation methods (short steps)

• For ointments: mix drug into melted base or use levigation to reduce particle size before incorporation.
• For creams (emulsions): prepare oil and aqueous phases, heat, then slowly combine with agitation to form a stable emulsion.
• For gels: dissolve gelling agent (e.g., carbomer, cellulose derivatives) in the liquid phase and neutralize if required to form gel structure.

Stability and preservation (practical notes)

• Water-containing formulations (creams, gels) require preservatives to prevent microbial growth.
• Ointments with water-free bases are less prone to microbial contamination.
• pH and ionic strength can affect stability of emulsions and gels.

Application and patient counseling (concise tips)

• Apply a thin layer and rub in if appropriate; inform about potential for staining garments (ointments are greasy).

• For infected lesions or weeping wounds, prefer water-washable bases and appropriate antimicrobial therapy.

• Key terms to remember: ointment, cream, gel, occlusive.

9 Suppositories and Inserts-1.pptx 🔺

• What this (typical) source would cover:
  • Definitions, bases, and routes for suppositories and vaginal/rectal inserts.
  • Methods of preparation, melting points, and factors affecting drug release from solid inserts.

Begin with the basic concept: what is a suppository/insert?

• A suppository is a solid dosage form intended for insertion into a body cavity (rectum, vagina, urethra) where it melts, softens, or dissolves to deliver drug locally or systemically.
• Inserts are compressed tablets or molded solids designed for vaginal or other mucosal insertion.

Types of bases and why they matter (simple explanation)

• Fatty/fat-soluble bases: cocoa butter (theobroma oil) or synthetic triglycerides — melt at body temperature to release drug.
• Water-soluble bases: polyethylene glycol (PEG) mixtures — dissolve rather than melt and are useful when a non-greasy residue is desired.
• Base choice influences melting behavior, drug release, and stability.

How drug is released (layered mechanism)

• For fatty bases: the base melts at body temperature and drug diffuses out into mucous/fluids.
• For water-soluble bases: base dissolves in fluids and drug is released by dissolution and diffusion.
• Drug solubility in the base and in body fluids, and the partition coefficient between base and fluid, determine release rate.

Preparation methods (step sequence)

1. Fusion (melt-and-pour): melt base, disperse or dissolve drug uniformly, pour into molds and cool to solidify.
2. Compression molding: force wetted powder blend into molds under pressure (used for thermally sensitive drugs).
3. Hand-rolling and shaping (small-scale/non-industrial): form the desired shape and size.

Dosing, shape, and packaging (practical points)

• Suppository sizes vary by route and patient population (infant vs adult).
• Provide lubrication instructions and storage recommendations (some bases melt at room temperature; refrigerate if necessary).
• Label with route of administration and special instructions (remove wrapper, warm between hands to ease insertion if needed).

Stability and special considerations

• Some drugs may migrate in a base (risk of instability) or interact with the base.

• Cocoa butter has polymorphic forms (different melting points) — proper cooling/tempering is important to prevent softening at room temperature.

• Key terms to memorize: suppository, fusion, base.