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Continuing our BCS topic, this week we will look at Class 3, Low Permeability, High Solubility drugs.
The bioavailability of Class 3 drugs is limited by the drug's permeability in the GI tract. Class 3 involves drugs in which the permeability is limiting but solubility is fine. The drugs are sufficiently soluble to be available in the GI tract.
List of Class 3 Drugs
A list of Class 3 drugs gathered from several sources includes the following:
| Acyclovir | Cefazolin | Gabapentin |
| Alendronate | Cetirizine | Hydralazine |
| Amiloride | Cimetidine | Metformin |
| Amlodipine | Ciprofloxacin | Metoclopramide |
| Amoxicillin | Cloxacillin | Minocycline |
| Atenolol | Codeine | Morphine |
| Atropine | Dicloxacillin | Neomycin B |
| Bisphosphonates | Enalaprilat | Peptides |
| Bidisomide | Erythromycin | Procainamide |
| Captopril | Famotidine | Ranitidine |
Compounding Considerations for BCS Class 3 Drugs
With Class 3 drugs, the issue is how to overcome the poor permeability of these compounds. An absorption enhancer may be necessary to overcome the poor permeability characteristics of these compounds.
Permeability is the rate-controlling step in drug absorption. Regarding permeability, a drug is considered highly permeable if the extent of intestinal absorption is found to be 90% or higher. Otherwise, the drug is considered poorly permeable. Regarding bioavailability, both the rate and extent of drug absorption may be highly variable for this class of drugs. If dissolution is fast (85% dissolved in less than 15 minutes), rather than dosage-form factors the variation will be due to:
- Variable GI transit
- Luminal contents
- Membrane permeability
Generally, this class may not be able to permeate the GI wall sufficiently fast for complete absorption.
Since absorption is permeation-rate limited, bioavailability is independent of drug release from the dosage form. Also, this class is problematic for controlled-release development.
For commercial drug product development, the following have been considered and some are appropriate considerations for compounding:
- Manipulate the site or rate of exposure for absorption
- Maximize local luminal concentration
- Incorporate functional agents into the dosage form to modify the metabolic activity of the enzyme systems
- Gastric retention systems
- Proteins and peptide drug delivery systems
- Incorporate permeability enhancer(s)
Examples of permeation enhancers that can be formulated into the dosage form include:
- Synthetic surfactants (SLS, polysorbate 20 and 80, glyceryl monolaurate)
- Bile salts (sodium deoxycholate)
- Fatty acids and derivatives (oleic acid, caprylic acid)
- Chelators (sodium EDTA, citric acid)
- Inclusion complexes (cyclodextrins and derivatives)
- Mucoadhesive polymers (polycarbophil, chitosan)
Next week, we will look at more detail for Class 4 drugs.
Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition
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