Abu Alam Ph.D.

1
Abu Alam Ph.D.

• Advisory Committee for Pharmaceutical Science
• and Clinical Pharmacology
• July 23, 2008

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Locally Acting Oral Drugs

• For the Treatment of Gastrointestinal Conditions

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Drug Substance

• Purity
• Impurity
• Molecular Size
• Solubility (pH 1 to 8)
• Permeability
• Degradation
• Analytical Method
• Specification
• Stability

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Dosage Form

• Formulation
• Excipients
• Manufacturing process
• Dosage form design
• Tablet
• Capsule
• Specifications
• Stability

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Schematic of GI Transit
Oral Dosage
Stomach pH 1.2
Duodenum pH 4.5
Elimination Feces
Colon pH 7.5
Jejunum pH 6.8
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Dissolution Illustrations USP Method I or II pH
1.2 (Sodium Chloride)
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Dissolution Illustrations USP Method I or II pH
4.5 (Acetate Buffer)
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Dissolution Illustrations USP Method I or II pH
6.8 (Phosphate Buffer)
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Schematic of Disposition
Oral Dosage
Dissolution GI Tract
Local Action GI Tract
Elimination Feces
Systemic Absorption
Systemic Toxicity
Elimination
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Criteria

• Not specifically absorbed
• Local action
• Dissolution is pH independent
• Freely available at site of action
• No permeation
• Vancomycin capsule fits the criteria

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Conclusion

• Comparative, superimposable dissolution profile
• Rate and extent of dissolution are same
• In Vivo bioequivalency is unnecessary
• Clinical trial to prove safety and efficacy are
  unnecessary