In Vitro and In Vivo Studies of a Verapamil-Containing Gastroretentive Solid Foam Capsule.

Ádám Haimhoffer,István Budai,Dávid Sinka,Ferenc Fenyvesi,Monika Béresová,Judit Váradi,Norbert Németh,Miklós Vecsernyés,Gábor Vasvári,Ildikó Bácskay,Ádám Deák

doi:10.3390/pharmaceutics14020350

Abstract

Gastroretentive systems may overcome problems associated with incomplete drug absorption by localized release of the API in the stomach. Low-density drug delivery systems can float in the gastric content and improve the bioavailability of small molecules. The current publication presents verapamil–HCl-containing solid foam prepared by continuous manufacturing. Production runs were validated, and the foam structure was characterized by micro-CT scans and SEM. Dissolution properties, texture changes during dissolution, and floating forces were analyzed. An optimized formulation was chosen and given orally to Beagle dogs to determine the pharmacokinetic parameters of the solid foam capsules. As a result, a 12.5 m/m% stearic acid content was found to be the most effective to reduce the apparent density of capsules. Drug release can be described by the first-order model, where 70% of verapamil dissolved after 10 h from the optimized formulation. The texture analysis proved that the structures of the solid foams are resistant. Additionally, the floating forces of the samples remained constant during their dissolution in acidic media. An in vivo study confirmed the prolonged release of the API, and gastroscopic images verified the retention of the capsule in the stomach.

Highlights

Eur. grade polyethylene glycol 4000 (PEG 4000), stearic acid type 50 (SA), and verapamil–HCl were acquired from Molar Chemicals Ltd. (Halásztelek, Hungary), while all other analytical grade chemicals were from Sigma-Aldrich Ltd. (Budapest, Hungary)
During the production of verapamil solid foam, the foam cell temperature was higher by 2 ◦ C than that previously described with the BaSO4 composition due to the higher melting point of the verapamil mixture [3,24]
Micro-CT scans revealed a closed cell structure where the main fraction of the voids was smaller than 120 microns

Summary

Introduction

One of the most important challenges in pharmaceutical technology is the development of drug delivery systems (DDS). The first and second generations include conventional therapeutic drug carriers such as tablets, capsules, granules, or their enteric coating versions. The group of controlled DDS is the third generation, which is a focus due to the reduced dosing frequency or enhanced drug efficacy compared with conventional formulations [1]. The number of newly synthesized active ingredients has decreased in recent decades, and the emphasis has been on converting existing active ingredients into renewed dosage forms.

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