Formulation Development Strategy for BCS Class III Molecules

For BCS Class 3 drugs, which are characterized by high solubility but low permeability, the primary formulation approach focuses on enhancing their permeability to improve bioavailability. Here are strategies tailored to different dosage forms:

Oral Solid Dosage Forms

Permeation Enhancers: Adding permeation enhancers like surfactants, bile salts, or certain excipients can improve the drug’s permeability in the gastrointestinal tract.

Prodrugs: Designing a prodrug that is more permeable can help bypass the permeability issue, converting to the active drug in the body.

Complexation: Cyclodextrin complexes or ion-pairing techniques can help increase permeability.

Gastroretentive Systems: For drugs absorbed primarily in the upper GI tract, gastroretentive systems (e.g., floating tablets) can prolong residence time and enhance absorption.


Oral Liquid Dosage Forms

Use of Micelles or Lipid-based Carriers: Lipid-based formulations, micelles, or microemulsions can increase permeability by altering the membrane structure or solubilizing the drug in a way that facilitates transport across the GI membrane.

pH Modulation: Adjusting the pH of the formulation can improve the drug’s permeability by ensuring it’s in a form that better penetrates the intestinal membrane.


Injectables

Nanotechnology: Nanoparticles or nanoemulsions can be used to increase the permeability and bioavailability of Class 3 drugs by targeting specific tissues or improving cellular uptake.

Liposomes: Encapsulating the drug in liposomes can increase permeability and deliver it directly to the target site, bypassing some permeability issues.

Permeability Enhancers: In injectables, co-administration of absorption enhancers may help in tissues with natural barriers, like subcutaneous or intramuscular administration sites.


Topical and Transdermal

Penetration Enhancers: Alcohols, terpenes, and fatty acids can disrupt the stratum corneum and enhance the drug’s permeability through the skin.

Nanoparticles and Liposomes: These can be applied to improve skin penetration by using drug carriers designed for small particle size.

Ionophoresis or Electroporation: These techniques use electric fields to enhance permeability, ideal for drugs with low natural permeability.


Inhalation Dosage Forms

Permeation Enhancers for Lung Absorption: Use of permeation enhancers, such as surfactants, to increase permeability in lung tissues.

Micronization: Reducing particle size to improve deposition in lung tissues and, therefore, increase surface area and permeability.

Lipid-based Carriers: Formulating the drug in lipid carriers, such as liposomes or nanoparticles, to improve absorption across the pulmonary barrier.

For BCS Class 3 drugs, a combination of formulation techniques that enhance permeability and optimize drug absorption site targeting can be most effective across different dosage forms.


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Resource Person: Moinuddin syed. Ph.D, PMP®

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