ceutics 1

Pharmaceutics

Pharmaceutics is a multifaceted discipline that integrates principles from physical pharmacy, pharmaceutical formulation, manufacturing technology, dispensing pharmacy, and legal aspects of pharmaceutics.

Goal of Pharmaceutics

To develop drug products that are effective, safe, and of high quality, whether they are intended for human or veterinary use.

Active Pharmaceutical Ingredient (API)

The main ingredient in a medicine that causes the desired effect of the medicine.

API

Also called drug substance and pharmacologic substance; the biologically active component of a drug product that produces the intended effects.

Drug Substance

Another term for Active Pharmaceutical Ingredient (API).

Pharmacologic Substance

Another term for Active Pharmaceutical Ingredient (API).

API — Additional Information

Some medicines contain more than one active pharmaceutical ingredient that act in different ways in the body.

API — Examples of Drug Products

Tablet, capsule, cream, injectable.

Physical and Chemical Characteristics of the API

Properties that influence dosage form development, including intrinsic solubility, pKa, membrane permeability, stability, and crystal characteristics.

Intrinsic Solubility

Crucial for determining how well a drug dissolves in biological fluids; influences the drug's bioavailability and therapeutic efficacy.

pKa

The pKa of a drug affects its ionization state in different pH environments.

Membrane Permeability

The ability of the drug to traverse biological membranes; essential for systemic absorption and efficacy.

Stability

An API property that is especially important in the presence of excipients.

Crystal Characteristics

Crystalline habit, particle size, and shape can influence the drug's dissolution rate, stability, and overall performance.

Intended Use of the Dosage Form

A factor influencing dosage form development.

Duration of Drug Release

May range from immediate to extended release.

Gastrointestinal Stability

Stability in the GIT is essential to ensure the drug is not degraded before absorption.

Ease of Administration

The dosage form must be suitable for the intended route of administration, considering factors like volume limitations and ease of use.

Dosage Form Limitations

Examples include size of tablets or capsules, injection volume, and application site; these must be addressed to ensure the product's practicality and effectiveness.

Excipients

Non-active components added to a dosage form to facilitate drug delivery; they play roles in drug release, stability, and patient acceptability.

Formulation and Excipients

The formulation must be carefully designed to ensure that the drug is delivered effectively.

Method of Manufacture

The method used to produce the dosage form can significantly affect its quality and performance.

Manufacturing Process

Includes considerations of equipment, process controls, and adherence to good manufacturing practices (GMP).

Good Manufacturing Practices (GMP)

Practices involving equipment, process controls, and proper manufacturing procedures to help ensure dosage-form quality and performance.

Formulation Challenges in Veterinary Medicine

The formulation of veterinary medications involves unique challenges compared to human pharmaceuticals.

Species-Specific Needs

Considerations include species, breed variations, body sizes, and feeding habits.

Herd Health Considerations

Must address logistical challenges and cost-effectiveness, environmental safety, and human food safety.

Disease States

The health condition can affect drug intake and pharmacokinetics.

Variety of Dosage Forms in Veterinary Medicine

Includes oral dosage forms, injectable formulations, medicated powders and drenches, medicated articles, topical products, transdermal products, transvaginal products, and rumen boluses.

Oral Dosage Forms

Include tablets and capsules, and oral solutions and suspensions.

Tablets and Capsules

Solid dosage forms for easy administration and precise dosing.

Oral Solutions and Suspensions

Liquid forms for animals that cannot take solid forms or require large doses.

Injectable Formulations

Include solutions and suspensions that can be either immediate release or sustained release.

Solutions and Suspensions

Injectable forms that can be either immediate release or sustained release.

Sustained-Release Formulations

Designed for prolonged drug action.

Medicated Powders

Added to drinking water for herd-wide administration.

Drenches

Large-volume aqueous suspensions or solutions administered directly into the rumen.

Medicated Articles

Type A Medicated Articles are concentrated formulations mixed with feed for animal consumption.

Type A Medicated Articles

Concentrated formulations mixed with feed for animal consumption.

Topical Products

Include skin, ophthalmic, otic, and intramammary products for localized treatment.

Skin Products

Topical products used for localized treatment.

Ophthalmic Products

Topical products used for localized treatment.

Otic Products

Topical products used for localized treatment.

Intramammary Products

Topical products used for localized treatment.

Transdermal Products

Products that deliver drug systemically through the skin.

Transdermal Patches

Provide systemic absorption through the skin.

Transvaginal Products

Products that provide systemic drug absorption via the vaginal epithelium.

CIDR (Controlled Internal Drug Release)

Provides systemic drug absorption via the vaginal epithelium.

Rumen Boluses

Large tablets that provide immediate or extended drug release within the rumen.

Understanding the Active Pharmaceutical Ingredient (API)

Before developing a pharmaceutical product, it is crucial to understand the physical and chemical properties of the API.

Most APIs

Most APIs are solid materials, either crystalline or amorphous, though biomass products require careful control during production.

Key Properties of APIs

1. Purity

2. Physicochemical Characteristics

Purity

Essential for accurate identification and consistent chemical, physical, and biological properties.

Physicochemical Characteristics

Include rheology, particle size, crystalline structure, melting point, intrinsic solubility, solid-state properties, partition coefficient, pKa, stability, and ionization constants.

Critical Quality Attributes (CQAs)

Properties defined by integrating knowledge of API characteristics; they help optimize formulation and ensure the API can effectively reach its site of action and elicit the desired biological response.

Crystalline Form

APIs often form crystalline structures during synthesis.

Factors Influencing Crystal Formation

Solvent system, temperature, pressure, cooling rate, and time.

Crystal Lattice

Composed of repeating units called unit cells.

Strong Crystal Lattice

Has higher melting points and is less soluble.

Weak Crystal Lattice

Has lower melting points and is more soluble but less stable.

Amorphous State

Characterized by random atomic arrangement, higher solubility, but lower stability.

Amorphous Forms

Can recrystallize in vivo, leading to solubility and bioavailability issues.

Polymorphism

The ability of a drug to exist in multiple crystalline forms, each with distinct lattice arrangements.

Impact of Polymorphism

Different polymorphs can affect solubility, dissolution rate, density, hardness, and crystal shape.

Anhydrous Forms

Generally have higher solubility compared to hydrates.

Examples of Polymorphic Drugs

Theophylline, ampicillin, and caffeine.

Theophylline

An example of a drug that exhibits polymorphism with differences in solubility and dissolution characteristics among its forms.

Ampicillin

An example of a drug that exhibits polymorphism with differences in solubility and dissolution characteristics among its forms.

Caffeine

An example of a drug that exhibits polymorphism with differences in solubility and dissolution characteristics among its forms.

Solvates

Crystalline solids with incorporated solvents.

Hydrates

Solvates where the incorporated solvent is water.

Solubility of Anhydrous Forms

Generally, anhydrous forms are more soluble than hydrates due to the stability of their crystalline arrangement.

Polymorphism and Preformulation

Crucial for drug formulation because they impact bioavailability, stability, and physicochemical properties.

Techniques for Evaluation of Polymorphism

1. Hot stage microscopy

2. Thermal analysis

3. Infrared spectroscopy

4. Near infrared spectroscopy

5. X-ray diffraction spectroscopy

Hot Stage Microscopy

A technique used for evaluation of polymorphism.

Thermal Analysis

A technique used for evaluation of polymorphism.

Infrared Spectroscopy

A technique used for evaluation of polymorphism.

Near Infrared Spectroscopy

A technique used for evaluation of polymorphism.

X-ray Diffraction Spectroscopy

A technique used for evaluation of polymorphism.

Particle Size

Affects dissolution rate, content uniformity, taste, texture, color, and stability.

Effects of Reducing Particle Size

Reducing particle size increases surface area, decreases the diffusion boundary layer, and can enhance solubility.

Particle Size Reduction Methods

Shearing, impact, attrition, and compression.

Fine Particles

Particles less than 10 μm; tend to be cohesive and affect powder flow.

Particles ≥250 μm

Relatively free-flowing.

Smaller Particles

Generally improve blend uniformity.

Particle Shape

Affects mixing, tableting, and overall formulation properties.

Particle Shape Descriptors

Common shapes include acicular, flake, plate, lath, equate, and spherical.

Acicular

Needle-like, slender particles.

Flake

Thin, flat particles with similar length and width.

Plate

Flat particles with greater thickness than flakes.

Lath

Long, thin, blade-like particles.

Equate

Particles with similar length, width, and thickness.

Spherical

Globular-shaped particles.

Crystal Growth

Smaller particles can lead to crystal growth through Ostwald ripening and nucleation, affecting formulation stability.

Ostwald Ripening

A process involved in crystal growth that can occur with smaller particles and affect formulation stability.