Pharmaceutics II Final Study Guide Notes

Granules and Granulation Process

• Granules are defined as aggregates of powder particles formed by the granulation process.
• Common applications of granules include:
  • Making tablets
  • Filling capsules
• Binding agents are routinely used in the granulation process.

Granulation Materials and Methods

• The starting material in the granulation process is powder.
• Binding agents are added to promote aggregation.

Methods of Granulation

• The wet granulation method uses liquid bridging by wetting powder and a sieve to separate granules.
• The dry granulation method employs binding agents and compression at high pressure to form large tablets, which are then granulated by mills.

Tablet Preparation

• Compressed tablets are prepared with punches under very high pressure.
• Molded tablets are prepared by forcing dampened powder into a mold, involving much lower pressure (soft/rapidly dissolve).

Benefits of Tablet Coatings

• Benefits of tablet coatings include:
  • Provides strength to the tablet.
  • Can be used for product branding.
  • Separates incompatible materials.
  • Protects drug from light, moisture, and oxidation.
  • Masks unpleasant tastes or odors.

Coating Processes

• Sugar coating adds 30% to 50% extra mass to the tablets and involves the following steps:
  1. Seal tablet core
  2. Sub coating
  3. Smoothing
  4. Coloring
  5. Polishing
  6. Printing
• Film coating typically adds 2% to 3% to the tablet mass.

Coating Defects and Causes

• Match coating defects to their causes:
  • Peeling - Associated with a high degree of attrition and low polymer amounts.
  • Roughness - Due to inefficient drying.
  • Sticking & picking - Related to viscous formulation or rapid drying of droplets.
  • Twinning - Caused by improper tablet core temperature handling.
  • Chipping - Occurs with inappropriate tablet shapes.
  • Cracking - Related to inadequate film strength or adhesive failure.
  • Logo Bridging - Generally results from inadequate design and excessive viscosity.

Types of Capsules

• A capsule is a solid dosage form containing at least one APIs and/or inert substances enclosed in a small shell or gelatin capsule.
• Hard capsules consist of two cylindrical sections (body and cap) and are filled with powders and granules.
• Soft capsules have a continuous gelatin shell made softer by adding glycerol or sorbitol, which aids in swallowing.

Gelatin and HPMC

• Gelatin is produced from collagen via heating and is stable when dry and edible (nontoxic).
• HPMC (Hydroxypropyl Methylcellulose) is derived from plants and can be used in capsule production for patients with dietary restrictions.

Capsule Preparation Steps

• There are three steps required to prepare hard capsules.
• Capsule volume is inversely related to size number.
• Preparing soft gel capsules is a one-step process.

Immediate-Release vs. Modified-Release Dosage Forms

• Immediate-release forms taken more than once daily can cause peaks and valleys in therapeutic blood levels.
• Doses not administered on schedule may reflect less than optimum therapy.
• Modified-release forms aim to deliver drugs at desired rates and specific sites in the gastrointestinal tract.
• Most modified-release products are oral tablets and capsules; also include ocular, parenteral, subdermal, and vaginal products.

Release Characteristics

• Delayed-release refers to the timing of drug release after administration.
• Extended-release maintains sustained drug plasma levels for longer periods.
• Gastro-retentive systems prolong drug presence in the stomach.
• Repeat-action dosage forms contain two doses for immediate and delayed release.

Disadvantages of Modified-Release Forms

• Loss of flexibility in adjusting dosages (cannot split doses).
• Dose dumping can occur from improper coatings or if the dosage form is chewed or crushed.

Extended Release Systems

• Extended-release oral dosage forms maintain therapy levels over extended periods (up to 24 hours) and reduce the frequency of dosing.
• The release pattern is controlled consistently over time, often referred to as sustained-release and slow-release.

Matrix Systems and release Dynamics

• Hydrophilic matrix systems are a cost-effective method for extended-release systems, often using HPMC as the primary polymer.
• As the tablet absorbs water, a gel layer forms which regulates drug release.
• Insoluble matrix systems maintain integrity throughout the GI tract and are expelled unchanged in feces.
• Release rates depend on porosity and tortuosity of the matrix, with higher compaction forces leading to lower porosity and slower drug release.

Conclusion

• Understanding the various aspects of granulation, tablet and capsule preparation, and modified release is crucial for effective dosage form design in pharmaceuticals.

Key Polymer Properties and Functions

• Drug release control can be influenced by adjusting polymer properties such as:
  • Proportion or percentage of drug-polymer mixtures.
  • Structure and molecular weight of polymers.
  • Viscosity which affects dissolution and diffusion rates.