In vitro controlled drug release from loaded microspheres - dose regulation through formulation

Abstract

ABSTRACT-Purpose. Drug release profiles were established for ibuprofen encapsulated within several types of microspheres and a range of dissolution buffer media to study the effect these variables have in controlling the rate and extent of drug release. Methods. Fatty acid microspheres containing ibuprofen were prepared by a process previously developed and refined to produce microspheres of a known size and composition, namely 80-125 μm diameter and an excipient to ibuprofen ratio of 3:1. Drug release profiles from these encapsulated formulations were compared with those obtained for the dissolution of ibuprofen alone under the same conditions. Results. Stearic acid microspheres were found to only partially retard the release of ibuprofen over a twenty minute period compared with the dissolution of ibuprofen alone. However, a significant retardation of ibuprofen release was observed with cetostearyl alcohol microspheres over the same period of time. Secondly, drug release profiles for encapsulated ibuprofen were determined using five distinct dissolution buffer media; sodium phosphate, potassium phosphate, citric acid and phosphate mix, MOPS and tris. Significant differences in the extent and rate of drug release were recorded between the different dissolution buffer solutions. These differences were also shown to be independent of variations in pH, temperature, buffer concentrations and the type of cations present. Conclusions. The presence and choice of microsphere formulation, and the choice of buffer present in the dissolution solution, can influence drug release in vitro, i.e. it is possible to achieve controlled drug release from microspheres. To explain the control achieved through the choice of buffer in solution it is proposed that the buffer anion exerts a stabilising influence on the ibuprofen-microsphere matrix. NOVELTY OF THE WORKThe research presented in this paper introduces a new formulation for pharmaceutical applications, namely encapsulating a drug within stearic acid and cetostearyl alcohol microspheres. Several interesting observations were made in that different microsphere formulations retarded drug release in vitro to differing degrees and surprisingly, the buffer anion appeared to dictate drug release. It is therefore now possible to produce a unique formulation with a highly controlled level of drug release, i.e. achieving dose regulation through formulation.

Controlled Microwave Processing Applied to the Pharmaceutical Formulation of Ibuprofen

“…One particularly interesting difference is observed when comparing the initial drug release profiles using microwave heating with stearic acid. With water present in the formulation process, it would appear that there is an initial burst effect as drug is released rapidly, this agrees with published data (14). However, this is not observed when water is absent in the formulation process and further work is currently in progress to investigate this phenomenon further.…”

“…Under certain conditions, stearic acid forms drug-loaded microspheres, previously exemplified using cefuroxime axetil (13). To form drug-loaded microspheres requires a heating stage, thus justifying this excipient choice (14). In comparison, PVP forms a cross-linked matrix that has been shown to constrain drugs in stable molecular clusters (15).…”

Toward Improving Medication Adherence: The Suppression of Bitter Taste in Edible Taste Films

“…A drug delivery system that provides a therapeutic agent in the correct dosage, in a manner that optimizes efficacy, minimizes bitter taste perception, and decreases choking hazards, is predicted to increase drug compliance in young children [ 28 , 29 ]. One promising approach to this problem is to encapsulate a bitter tasting compound within fatty acid microspheres [ 30 , 31 ].…”

“…Stearic acid is a promising fatty acid for encapsulating drugs because this saturated long-chain biocompatible fatty acid exhibits minimal taste [ 32 ], functions as a solid carrier for drugs [ 33 ], melts at a temperature that is suitable for encapsulating compounds [ 31 ], and is resistant to decomposition at high temperatures [ 34 ]. In addition, dietary stearic acid has a neutral effect on serum low-density lipoprotein levels [ 35 ].…”

Effect of production variables on the physicochemical characteristics of celecoxib-loaded stearic and alginic acids-based microparticles

“…Among the various solid lipids that have been shown to prepare microparticles, the fatty acid like stearic acid is particularly recognized because of its favorable biocompatible properties and availability in cheaper cost in comparison to synthetic polymers. However, preparing the microparticles based on stearic acid alone as matrix former and by the use of the aqueous-based methods usually resulted in the formation of irregular/nonspherical particles [3]. In an attempt to prepare stearic acid-based microparticles with spherical shape, anionic polysaccharide such as alginic acid was added in the current investigation.…”