conclusion ba ce2

Conclusion — Dosage Forms

Each dosage form, whether solid or semisolid, presents unique challenges and benefits. Understanding these characteristics is essential for optimizing drug delivery in veterinary medicine and ensuring each animal receives the most effective and safe treatment possible.

Development and Manufacturing of Chewable Tablets for Companion Animals

Chewable tablets for companion animals, particularly dogs and cats, have evolved significantly since their inception in the 1960s. Initially modeled after human pharmaceutical products, they have undergone improvements in palatability, manufacturing processes, and quality control to meet the specific needs of companion animals.

Historical Development of Chewable Tablets

Chewable veterinary tablets developed significantly from the 1960s onward, with improvements in formulation, palatability, flavoring agents, manufacturing processes, and quality control.

Early Development of Chewable Tablets (1960s–1970s)

The first chewable veterinary tablets were produced using standard pharmaceutical equipment, mainly through wet granulation using water and corn syrup.

Early Canine Palatability

Early canine chewable tablets had palatability scores of 70–85%.

Early Feline Palatability

Early feline formulations struggled with palatability, often scoring less than 50%.

Flavor Experiments in the 1980s

Milk and cheese flavors were tested. Canine palatability never exceeded 80%, while feline palatability reached only 70%. Garlic, although considered palatable to dogs, resulted in poor acceptance rates of 30–60%.

Challenges with Early Chewable Tablet Formulations

Quality of palatability enhancers, rancidity issues, and microbial contamination.

Quality of Palatability Enhancers

Early formulations included animal by-products of questionable quality, such as bovine liver extracts, fish meal, and other ingredients unsuitable for human consumption.

Rancidity Issues in Early Formulations

The high fat content in flavoring ingredients led to stability problems, including rancidity, even when stabilized with antioxidants.

Microbial Contamination in Early Chewable Tablets

High microbiological counts, such as E. coli and Salmonella, were common. This could cause chewable tablets to change from brown to green and emit offensive odors.

Advancements in the 1990s and Beyond

The industry shifted toward improved flavoring agents that provided better aroma and taste, along with higher quality standards.

Improved Flavoring Agents — Development

In the early 1990s, the industry shifted toward developing chewable tablets with improved flavoring agents that provided better aroma and taste.

Improved Flavoring Agents — Quality Standards

Modern flavoring agents meet human food-grade and/or pharmaceutical-grade quality standards, ensuring stability, consistency, and minimal microbial contamination.

BRAVECTO

BRAVECTO (fluralaner) was approved by the FDA in 2014 and was the first chewable tablet for dogs shown to kill fleas and multiple tick species for 12 weeks in a single dose.

Manufacturing Processes for Chewable Tablets

Direct compression; wet and dry granulation; extrusion and forming machines; and curing.

Direct Compression for Chewable Tablets

A simple manufacturing method requiring minimal capital investment and ideal for producing chewable tablets quickly and efficiently.

Wet and Dry Granulation for Chewable Tablets

Wet granulation uses appropriate solvents, while dry granulation involves slugging or roller compaction.

Extrusion and Forming Machines

Dough formed from milled and blended ingredients is shaped using forming machines, producing various shapes and sizes, with weights up to 15 g.

Curing of Chewable Tablets

Curing may be done by oven curing or room temperature curing.

Oven Curing

Tablets are cured in an oven at 40–50°C.

Room Temperature Curing

Tablets are left at room temperature with relative humidity of 40–70% for up to 7 days, depending on the formulation.

Critical Variables in Tablet Formulation

Tablet weight and hardness are key factors influencing the palatability and acceptance of chewable tablets, especially for felines.

Feline Chewable Tablet — Ideal Hardness Range

The ideal hardness range is 3–4 Kp.

Feline Chewable Tablet — Hardness Above 6 Kp

Palatability decreases significantly when hardness exceeds 6 Kp.

Feline Chewable Tablet — 6 Kp vs. 12 Kp

A feline chewable tablet with 6 Kp hardness might have 95% free-choice acceptance, but this drops to 50% when hardness increases to 12 Kp.

Critical Quality Attributes (CQAs) of Chewable Tablets

Appearance; Assay and Content Uniformity; Dissolution; Impurities; and Loss on Drying.

Appearance — Chewable Tablets

Visual consistency and appeal of the tablets.

Assay and Content Uniformity — Chewable Tablets

Ensuring each tablet contains the correct dosage of the active pharmaceutical ingredient (API).

Dissolution — Chewable Tablets

The rate at which the tablet dissolves in the animal's gastrointestinal tract, affecting the drug's bioavailability.

Impurities — Chewable Tablets

Minimizing the presence of contaminants to ensure safety and efficacy.

Loss on Drying — Chewable Tablets

Controlling moisture content to maintain tablet stability.

Kilopond (kp)

A unit of force also called a kilogram of force. It should not be confused with a pound.

Other Solid Dosage Forms

Solid dosage forms include capsules, powders, granules, medicated feeds, and biomass products, with different formulations, advantages, challenges, and quality attributes.

Capsules

Solid dosage forms in which the drug is enclosed in a soluble shell, typically made from gelatin, cellulose, or polymeric material.

Types of Capsules

Hard capsules and soft capsules.

Hard Capsules

Two-piece capsules consisting of a body and a cap, filled with powder or beads.

Hard Capsules — Applications

Often used for extended drug release, utilizing technologies such as beads and osmotic pumps.

Soft Capsules

Single-piece capsules filled with a solution or suspension containing the active pharmaceutical ingredient (API).

Soft Capsules — Applications

Commonly used for poorly water-soluble drugs to enhance in vivo dissolution and ensure content uniformity.

Hard vs. Soft Capsules — Interaction Risks

Soft capsules have more intimate contact between the shell and liquid contents, increasing the risk of undesirable interactions, such as gelatin crosslinking and pellicle formation.

Quality Attributes of Capsules

Assay; Content Uniformity; Impurities; and Dissolution.

Assay — Capsules

Measuring the drug content to ensure correct dosage.

Content Uniformity — Capsules

Ensuring consistent distribution of the API in each capsule.

Impurities — Capsules

Monitoring and minimizing contaminants.

Dissolution — Capsules

Assessing how quickly and completely the drug dissolves in the animal's gastrointestinal tract.