Dosage Forms and Drug Stability Exam Review

Comprehensive vocabulary flashcards covering drug degradation pathways, chemical kinetics, liquid and coarse dispersions, micromeritics, powder properties, granulation techniques, and capsule formulations from the lecture notes.

Glass transition temperature ($T_g$)

An important property of amorphous materials. Below $T_g$, molecules are relatively rigid with limited mobility; above $T_g$, molecular mobility increases, making recrystallization more likely.

Hygroscopic

Describes a substance that absorbs moisture from the air.

Deliquescent

Describes a substance that absorbs so much moisture from the air that it dissolves in the absorbed water.

Hydrate

A crystalline form in which water molecules are incorporated directly into the crystal lattice.

Solvate

A crystalline form in which non-water solvent molecules are incorporated into the crystal lattice.

Anhydrous

A crystalline form that has no water incorporated into its crystal structure.

Eutectic mixture

A combination of substances that melts at a temperature lower than the melting points of the individual components.

Aerosolization

In dry powder inhalers (DPIs), the process where strong, rapid inhalation lifts the powder from the device.

De-aggregation

In dry powder inhalers (DPIs), the process where turbulence separates small drug particles ($1\text{--}5\,\mu\text{m}$) from larger carrier particles ($50\text{--}200\,\mu\text{m}$).

Hydrolysis

A chemical degradation pathway in which water participates in breaking susceptible chemical bonds, particularly vulnerable groups such as esters, amides, lactams, and lactones (e.g., aspirin degrading to salicylic acid and acetic acid).

Oxidation

A chemical degradation pathway in which oxidative reactions chemically alter the drug; common in catechols, phenols, thiols, and unsaturated groups, often accelerated by oxygen, light, iron, copper, or peroxides (e.g., epinephrine turning pink or brown).

Photolysis

Chemical degradation caused directly or through photo-oxidation by UV or visible light (e.g., nifedipine, sodium nitroprusside, and tetracyclines), requiring protection like amber bottles or opaque packaging.

Racemization / Isomerization

A degradation pathway where a drug changes its stereochemical or structural form without fragmenting, potentially altering its pharmacological activity (e.g., epinephrine under strongly acidic conditions).

Maillard reaction

A chemical reaction that produces browning when an amine-containing drug is combined with lactose.

pH adjustment

The formulation strategy of selecting a specific pH that minimizes drug degradation, noting that pH 7 is not automatically the most stable point.

Buffer

A formulation excipient that resists changes in pH, though certain buffers can catalyze drug degradation.

Antioxidant

An excipient that slows oxidative reactions and can be consumed over time, including chain-breaking agents (BHT, BHA, Vitamin E) and oxygen scavengers (ascorbic acid, sulfites).

Chelator

An excipient (such as EDTA) that binds catalytic metal ions like $\text{Fe}^{3+}$ and $\text{Cu}^{2+}$ to reduce degradation, but does not replace the need for protection against oxygen.

Preservative

An agent (such as benzalkonium chloride or parabens) that inhibits microbial growth, but does not prevent chemical degradation.

Expiration date

The date assigned to an unopened manufactured product based on the manufacturer's stability studies.

Beyond-use date (BUD)

The date assigned to a compounded preparation based on applicable compounding standards and stability information.

In-use / post-reconstitution period

The timeframe established for a manufactured product after opening or reconstitution, guided by the manufacturer's product-specific labeling.

Zero-order degradation

A degradation reaction where a constant amount of drug is lost over time, concentration vs. time yields a straight declining line, the rate is concentration-independent, and successive half-lives become shorter ($t_{1/2} = \frac{C_0}{2k}$).

First-order degradation

A degradation reaction where a constant percentage of drug is lost over time, $\ln(\text{concentration})$ vs. time yields a straight declining line, and the half-life remains constant ($t_{1/2} = \frac{0.693}{k}$).

$$t_{90}$$

The time required for a drug concentration to decrease to 90% of its initial value, indicating that 10% has degraded.

Arrhenius equation

The relationship $k = A e^{-E_a/(RT)}$, which describes how the degradation rate constant ($k$) increases exponentially with increasing absolute temperature ($T$).

V-shaped pH-rate curve

A degradation profile showing acid catalysis at low pH, base catalysis at high pH, and a nadir (bottom of the V) where the degradation rate constant ($k_{\text{obs}}$) is lowest, representing maximum stability.

Solution

A homogeneous, single-phase liquid dosage form in which drug molecules are completely dissolved; precipitation is the primary physical instability risk.

Suspension

A heterogeneous, two-phase dosage form containing insoluble solid drug particles dispersed in a liquid vehicle; sedimentation and caking are major stability risks, requiring shaking before dosing.

Emulsion

A heterogeneous, two-phase dispersion of two immiscible liquids (such as oil and water) stabilized by an emulsifier, vulnerable to creaming, coalescence, and cracking.

Tyndall effect

The phenomenon of light scattering by particles in a colloidal dispersion ($1\text{--}1000\,\text{nm}$), rendering the light beam visible.

Flocculated suspension

A suspension characterized by loose clusters of particles (flocs) that settle rapidly into an easily redispersible, loose sediment, providing reliable dose uniformity.

Deflocculated suspension

A suspension characterized by individually dispersed particles that settle slowly into a dense, compacted layer with a high risk of irreversible hard caking.

Creaming

An emulsion instability where droplets rise or sink due to density differences between phases; usually reversible with gentle shaking.

Coalescence

An emulsion instability where dispersed droplets fuse to form larger droplets; a progressive, concerning process that leads to irreversible failure.

Cracking / breaking

Permanent, irreversible phase separation of an emulsion into completely distinct liquid layers.

Phase inversion

The phenomenon where an emulsion shifts from oil-in-water (O/W) to water-in-oil (W/O), or vice versa, depending on formulation factors.

Surfactant

An amphiphilic substance that lowers interfacial tension between phases, serving to wet hydrophobic drug particles in suspensions or stabilize droplet interfaces in emulsions.

HLB (Hydrophilic-Lipophilic Balance)

A numerical scale indicating surfactant characteristics: 3–6 is more lipophilic (W/O emulsifier), 7–9 is intermediate (wetting agent), and 8–18 is more hydrophilic (O/W emulsifier).

Zeta potential

A measurement of the electrostatic potential related to particle repulsion; values greater than $+30\,\text{mV}$ or less than $-30\,\text{mV}$ provide strong repulsion, while values near $0\,\text{mV}$ promote aggregation.

Gold Number

A metric reflecting the effectiveness of a protective colloid; lower numbers denote stronger protective capability against aggregation (e.g., gelatin is 0.005–0.01 vs. potato starch at 20–25).

Micromeritics

The science and technology of small particles, including both fundamental properties (size, shape, surface area) and derived properties (density, porosity, flow).

Noyes-Whitney equation

The mathematical model $\frac{dC}{dt} = \frac{DA(C_s - C)}{hV}$ describing solid drug dissolution rate as a function of diffusion coefficient, surface area, solubility gradient, diffusion layer thickness, and medium volume.

Segregation (Demixing)

The unwanted physical separation of different particle sizes or densities during powder handling, leading to poor content uniformity in tablets or capsules.

Bulk density

Powder mass divided by the total volume of the untouched powder bed, including void spaces between particles.

Tapped density

Powder mass divided by volume measured after mechanical tapping compacts the particles; generally greater than or equal to bulk density.

Bulkiness

The reciprocal of bulk density ($\frac{1}{\rho_{\text{bulk}}}$); describes the volume occupied per unit mass of powder.

Carr's index

A powder compressibility measure calculated as $\frac{\rho_{\text{tapped}} - \rho_{\text{bulk}}}{\rho_{\text{tapped}}} \times 100$; higher percentages signify higher cohesiveness and poorer flowability.

Hausner ratio

The ratio of tapped density to bulk density ($\frac{\rho_{\text{tapped}}}{\rho_{\text{bulk}}}$); higher values correlate with greater interparticle friction and poorer flow.

Angle of repose

The steepest angle formed by a poured powder heap relative to the horizontal plane; lower angles ($25\text{--}30^\circ$) reflect excellent flow, while higher angles ($56\text{--}65^\circ$) indicate very poor flow.

Granulation

The process of agglomerating smaller powder particles into larger, permanent granules to enhance flow, prevent demixing, and facilitate compression.

Wet granulation

A granulation technique involving liquid binder addition, massing, screening, drying, and sizing; not suitable for moisture- or heat-labile active ingredients.

Dry granulation

A granulation method that compacts dry powder mixtures under high mechanical pressure (via slugging or roller compaction) into compacts or ribbons that are milled into granules; ideal for moisture- or heat-sensitive drugs.

Fluid-bed granulation

An all-in-one granulation process where powder particles are suspended in an upward stream of conditioned air while liquid binder is sprayed, combining granulation and drying in a single vessel.

Bulk powders

Non-potent powder formulations packaged in multi-dose containers from which the patient measures individual doses.

Divided powders

Powder formulations partitioned into premeasured individual dose packets to provide precise dosing.

Dusting powders

Medicated powders intended for external application to the skin, formulated with fine particles to prevent grittiness and irritation.

Insufflations

Finely divided medicated powders intended to be blown into body cavities using a dedicated delivery apparatus.

Sieve number

A standardized rating of mesh size where a higher sieve number corresponds to smaller mesh openings (e.g., #8 is $2{,}360\,\mu\text{m}$, #20 is $850\,\mu\text{m}$, and #100 is $150\,\mu\text{m}$).

Hard gelatin capsule

A two-piece capsule (body and cap) typically containing dry solids (powders, granules, pellets), with a shell moisture content of 13–16% and no plasticizer.

Soft gelatin capsule

A one-piece, hermetically sealed capsule produced via a rotary-die process containing liquids, suspensions, or pastes, formulated with plasticizers (glycerin, sorbitol) and dried to 6–10% moisture.

HPMC capsule

A vegetarian capsule shell made from plant-derived hydroxypropyl methylcellulose containing approximately 4–6% moisture and inherently resistant to aldehyde-induced cross-linking.

Pullulan capsule

A vegetarian capsule shell produced through microbial fermentation to yield a natural polysaccharide alternative to animal-derived gelatin.

Gelatin cross-linking

A chemical reaction commonly triggered by exposure to aldehydes that forms covalent bonds within the gelatin shell, decreasing solubility and slowing drug dissolution.

DBcaps

Opaque, wide-diameter capsules engineered to blind intact tablets or comparative products during clinical trials.

Standard capsule size scale

The numerical sizing system for standard capsules, where size 000 is the largest and size 5 is the smallest.

Glidant

An excipient (such as colloidal silicon dioxide) that reduces interparticle friction to enhance the flow of powders into filling dies or capsule bodies.

Lubricant

An excipient (such as magnesium stearate) that reduces friction between moving machinery surfaces and the formulation powder blend.

Disintegrant

An excipient (such as sodium starch glycolate) that promotes rapid breakdown of a compressed or compacted powder mass upon exposure to moisture.

Plasticizer

An excipient (such as glycerin, sorbitol, or propylene glycol) added to capsule shells to increase wall flexibility and decrease brittleness.

Opacifier

An excipient (such as titanium dioxide) incorporated into capsule shells or coatings to render them opaque, shielding light-labile ingredients from degradation.