Optimizing Prednisolone Loading into Distiller's Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery.

Esther T L Lau,Deirdre Mikkelsen,Roger A Stanley,Elizabeth Mccourt,Barbara A Williams,Ram Mereddy,Kathryn J Steadman,Peter J Halley,Stuart K Johnson

doi:10.3390/pharmaceutics9020017

Abstract

Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT.

Highlights

Kafirin microparticles have been investigated for their potential as an oral delivery system.Kafirins are storage proteins of the sorghum grain, and their characteristic hydrophobic and poorly digestible nature [1,2,3] has been identified as a potential delivery system that can target or delay the release of medications
The Response surface methodology (RSM) models generated were inadequate for accurately predicting the relationship between the starting quantities of kafirin and prednisolone, and prednisolone loading and loading efficiency
The robustness of the model needs to be improved with better data before it can be used to predict optimal combinations to formulate kafirin microparticles loaded with prednisolone for use as an oral drug delivery system

Summary

Introduction

Kafirin microparticles have been investigated for their potential as an oral delivery system.Kafirins are storage proteins of the sorghum grain, and their characteristic hydrophobic and poorly digestible nature [1,2,3] has been identified as a potential delivery system that can target or delay the release of medications. Approximately 20–25% of the prednisolone loaded into microparticles made using kafirin extracted from whole grain sorghum, was released over seven hours in simulated gastric and small intestinal conditions. These results suggest the kafirin microparticles have potential as a colon-targeted delivery system since they can protect the majority of the encapsulated material from being released in the upper GIT [4]. Given the presence of the colonic (anaerobic) bacterial microbiota, and the resulting low redox, it is hypothesized that these disulfide bonds may be reduced (cleaved) upon entry to the colon, thereby releasing the encapsulated drug

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Conclusion