Oral dosage form formulation challenges
A) Poor Bioavailability
Many drugs face challenges in being absorbed through the gastrointestinal (GI) tract due to poor solubility, gastrointestinal pH, or presence of enzymes that degrade the drug before it can be absorbed into the bloodstream.
B) Solubility and Stability
1) solubility:
Drugs with low solubility may not dissolve sufficiently in the stomach or intestine to be absorbed effectively. Formulation strategies like solubilizing agents, co-solvents, or nanoparticle formulations are often required.
2) chemical stability:
Many drugs degrade in the acidic environment of the stomach or due to light/oxygen exposure. Ensuring the stability of the active pharmaceutical ingredient (API) throughout the product’s shelf life is a significant challenge.
C) Dosage Form Design
Tablets, capsules, or liquid forms each have their own set of challenges in terms of uniformity, dissolution rate, and ensuring a consistent dose.
Parenteral dosage form formulation challenges
A) Sterility and Contamination
1) Sterility Requirements:
Parenteral formulations must be sterile, as they bypass the body’s natural defenses. The formulation process must ensure the complete absence of bacteria, fungi, or endotoxins, which requires rigorous manufacturing conditions and quality control.
2) Packaging and Handling:
Sterile packaging (e.g., vials, ampoules, pre-filled syringes) must maintain the integrity of the formulation. Proper handling and storage, including temperature control (e.g., refrigeration), are critical to prevent contamination.
B) Formulation for High Concentration
Many biologic therapies require high concentrations of the active ingredient. However, achieving high concentrations while maintaining solubility and stability in the final formulation can be challenging.
C) Viscosity and Injectability
Viscosity Control: Parenteral formulations must be designed for easy injectability. Highly viscous solutions can be difficult to inject, especially for subcutaneous or intramuscular administration.
D) pH and Buffering
1) pH Sensitivity:
The pH of parenteral formulations is critical to maintaining stability and preventing irritation upon injection. A formulation that is too acidic or alkaline can cause pain or tissue damage at the injection site.
2) Buffering Agents:
Parenteral formulations often require buffering agents to maintain a stable pH. The choice of buffer is important because it must be compatible with the drug and safe for injection.
E) Storage and Stability
Parenteral formulations, especially biologics, are often sensitive to temperature and must be stored in controlled environments to avoid degradation.
Read also:
- Formulation Development Strategy for BCS Class IV Molecules
- Drug Excipient Compatibility Study During QbD
Resource Person: Hisham Ghazal