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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.