The Twofold Advantage of the Amorphous Form As an Oral Drug Delivery Practice for Lipophilic Compounds: Increased Apparent Solubility and Drug Flux Through the Intestinal Membrane

Overview

Journal AAPS J

Specialty Pharmacology

Date 2012 Dec 18

PMID 23242514

Citations 17

Authors

Arik Dahan

Avital Beig

Viktoriya Ioffe-Dahan

Riad Agbaria

Jonathan M Miller

Affiliations

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Abstract

The purposes of this study were to assess the efficiency of different nifedipine amorphous solid dispersions (ASDs) in achieving and maintaining supersaturation and to investigate the solubility-permeability interplay when increasing the apparent solubility via ASD formulations. Spray-dried ASDs of nifedipine in three different hydrophilic polymers, hydroxypropyl methylcellulose acetate succinate (HPMC-AS), copovidone, and polyvinylpyrrolidone (PVP), were prepared and characterized by powder X-ray diffraction and differential scanning calorimetry. The ability of these formulations to achieve and maintain supersaturation over 24 h was assessed. Then, nifedipine's apparent intestinal permeability was investigated as a function of increasing supersaturation in the parallel artificial membrane permeability assay model and in the single-pass rat intestinal perfusion model. The efficiency of the different ASDs to achieve and maintain supersaturation of nifedipine was found to be highly polymer dependent; while a dispersion in HPMC-AS enabled supersaturation 20× that of the crystalline aqueous solubility, a dispersion in copovidone enabled 10×, and PVP allowed supersaturation of only 5× that of the crystalline solubility. Nifedipine flux across the intestine from supersaturated solutions was increased, and the apparent intestinal permeability was constant, irrespective of the degree of supersaturation or the polymer being used. In conclusion, while with other solubility-enabling approaches (e.g., surfactants, cyclodextrins, cosolvents), it is not enough to increase the apparent solubility, but to strike the optimal solubility-permeability balance, which limits the chances for successful drug delivery, the amorphous form emerges as a more advantageous strategy, in which higher apparent solubility (i.e., supersaturation) will be readily translated into higher drug flux and overall absorption.

Citing Articles

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Amorphous Polymer-Phospholipid Solid Dispersions for the Co-Delivery of Curcumin and Piperine Prepared via Hot-Melt Extrusion.

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Microfluidics-on-a-chip for designing celecoxib-based amorphous solid dispersions: when the process shapes the product.

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Sweeteners Show a Plasticizing Effect on PVP K30-A Solution for the Hot-Melt Extrusion of Fixed-Dose Amorphous Curcumin-Hesperetin Solid Dispersions.

Wdowiak K, Tajber L, Miklaszewski A, Cielecka-Piontek J Pharmaceutics. 2024; 16(5).

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Emerging Applications of Hydroxypropyl Methylcellulose Acetate Succinate: Different Aspects in Drug Delivery and Its Commercial Potential.

Choudhari M, Damle S, Saha R, Dubey S, Singhvi G AAPS PharmSciTech. 2023; 24(7):188.

PMID: 37715004 DOI: 10.1208/s12249-023-02645-1.

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