Recent advances in testing of microsphere drug delivery systems

ABSTRACT

Introduction: This review discusses advances in the field of microsphere testing.

Areas covered: In vitro release-testing methods such as sample and separate, dialysis membrane sacs and USP apparatus IV have been used for microspheres. Based on comparisons of these methods, USP apparatus IV is currently the method of choice. Accelerated in vitro release tests have been developed to shorten the testing time for quality control purposes. In vitro-in vivo correlations using real-time and accelerated release data have been developed, to minimize the need to conduct in vivo performance evaluation. Storage stability studies have been conducted to investigate the influence of various environmental factors on microsphere quality throughout the product shelf life. New tests such as the floating test and the in vitro wash-off test have been developed along with advancement in characterization techniques for other physico-chemical parameters such as particle size, drug content, and thermal properties.

Expert opinion: Although significant developments have been made in microsphere release testing, there is still a lack of guidance in this area. Microsphere storage stability studies should be extended to include microspheres containing large molecules. An agreement needs to be reached on the use of particle sizing techniques to avoid inconsistent data. An approach needs to be developed to determine total moisture content of microspheres.

KEYWORDS:

• In vitro and in vivo release testing
• in vitro-in vivo correlation
• large molecule therapeutics
• microspheres
• physico-chemical properties
• storage stability study

Article highlights.

• Introduction to microspheres and microsphere characterization techniques

• Advances in characterization of various physicochemical properties of microspheres.

• Advances in in vitro/in vivo drug release testing of microspheres.

• Review of storage stability of various microsphere systems.

• Expert opinion on microsphere testing

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Declaration of interest

DJ Burgess and JV Andhariya were supported by Office of Generic Drugs/Office of Research Standards, USFDA (Grant Award 1U01FD004931-02). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.