Research Articles
Inhibiting the Gastric Burst Release of Drugs from Enteric Microparticles: The Influence of Drug Molecular Mass and Solubility

https://doi.org/10.1002/jps.22174Get rights and content

ABSTRACT

Undesired drug release in acid medium from enteric microparticles has been widely reported. In this paper, we investigate the relative contribution of microparticle and drug properties, specifically microsphere size and drug’s molecular weight and acid solubility, on the extent of such undesired release. A series of nine drugs with different physicochemical properties were successfully encapsulated into Eudragit S and Eudragit L microparticles using a novel emulsion solvent evaporation process. The process yielded spherical microparticles with a narrow size distribution (27–60 and 36–56 mm for Eudragit L and Eudragit S microparticles, respectively). Upon incubation in acid medium (pH 1.2) for 2 h, the release of dipyridamole, cinnarizine, amprenavir, bendroflumethiazide, budesonide and prednisolone from both Eudragit microparticles was less than 10% of drug load and conformed with the USP specifications for enteric dosage forms. In contrast, more than 10% of the entrapped paracetamol, salicylic acid and ketoprofen were released. Multiple regression revealed that the drug’s molecular weight was the most important factor that determined its extent of release in the acid medium, while its acid solubility and microsphere’s size had minor influences.

Section snippets

INTRODUCTION

The last two decades witnessed the emergence of microencapsulation technology in pharmaceutical formulations,1., 2. which provided a unique platform for delayed and site-specific oral drug delivery.3 Modified release microparticles provide several advantages over conventional enteric and delayed release formulations such as larger surface area, potentially more uniform gastric emptying, and a more consistent drug release profile. Unfortunately, the particulate nature and large surface area are

Materials

Paracetamol was supplied by Knoll AG (Ludwigshafen, Germany) and prednisolone was obtained from Sanofi-Aventis (Romainville, France). Budesonide and amprenavir were gifts from Astra Zeneca (Loughborough, UK), and GlaxoSmithKline (Harlow, UK), respectively. Ketoprofen, salicylic acid, dipyridamole, cinnarizine, bendroflumethiazide, sorbitan sesquioleate (Span 83, Arlacel 83) and liquid paraffin were purchased from Sigma-Aldrich (Poole, UK). Methacrylate polymers, Eudragit S and Eudragit L, were

Microsphere Properties

All nine drugs were successfully encapsulated into Eudragit L and Eudragit S microparticles. The particles were spherical and had a uniform size distribution of 27–60 and 36–56 mm for Eudragit L and Eudragit S, respectively (Tab. 1). Representative SEM images of amprenavir and prednisolone loaded microparticles are shown in Fig. 1. According to the SEM images, there was no evidence of porosity in any of the fabricated microparticles. In addition, X-ray powder diffraction and thermal analysis

CONCLUSIONS

Nine drugs with different chemical natures were encapsulated in Eudragit L and Eudragit S microparticles using a novel emulsion solvent evaporation method. This showed the universality of the employed method for the preparation of delayed release particulate formulations. The particles had the desirable properties of spherical morphology, smooth surface, small microsphere size (< 100 μm) and a uniform size distribution. However, all the drug-loaded microparticles did not conform to USP

REFERENCES (21)

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