Development Pharmaceutics of Microbicide Formulations. Part I: Preformulation Considerations and Challenges

Abstract

Microbicides, the compounds and formulations that can prevent transmission of sexually transmitted diseases (STDs)/HIV are being pursued actively as a promising AIDS intervention. The drug development chain for a topical microbicide differs significantly from that of any systemic or topical compound/formulation regarding to time line, cost, activities, and milestones. This is in part because of the lack of standard in vitro models to assess efficacy, and complex ethical issues in clinical trials of microbicides. Several factors, including changes in the physiology of the cervix and vagina with age and menstrual cycle, intercourse, as well as leakage of the formulation from the vagina may affect their design, development, and performance. Selection and development of optimal microbicide delivery systems (gel/cream, pessary, film, tablet, foam, etc.), their inactive ingredients, manufacturing details, and packaging system are dependent on the properties of active drug, or their preformulation parameters (PP). The PP of the active drug substance needs to be evaluated in initial stages of drug discovery and development so that the most suitable delivery system can be selected. Some PP of microbicide agents include physical state, organoleptic properties (color, odor, appearance, taste, etc.), molecular weight, aqueous solubility, hygroscopicity, acidity/alkalinity, permeability and absorption characteristics, stability in solid/solution state, and inherent bioadhesiveness. Thus, a well-coordinated, planned, and implemented preformulation program can help in not only accelerating microbicide formulation development, but also to minimize unforeseen failures in subsequent stages of the development. The objective of this review is to highlight the significance of PP, suggesting a systematic preformulation program.

Exploiting Drug Repositioning for Discovery of a Novel HIV Combination Therapy

“…Thus, the emergence of drug resistance limits potential drug therapies, making new anti-HIV therapies essential for successful long-term treatment of HIV infection. However, the development of novel anti-HIV drugs is costly (ϳ$600 million) and time-consuming (over 12 years) (12). One way to decrease the cost and expedite the development of novel drugs is to use a drug repositioning strategy which involves using drugs that are clinically approved for one condition to treat a different condition (1).…”

Periodontal Muco-Adhesive Formulations for the Treatment of Infectious Periodontal Diseases

“…Polymers properties such as swelling state, bioadhesive properties and the effect on the medium pH have significant importance for mucoadhesion. Some polymers may exhibit site specific mucoadhesive properties, thus the mucoadhesive properties should be evaluated and optimized with reference to physiological environments [53]. Mucoadhesive force can be studied by several in vitro and in vivo methods [49].…”

Effectiveness of female controlled barrier methods in preventing sexually transmitted infections and HIV: current evidence and future research directions

“…Though the majority of microbicide products are currently in preclinical development, 36 18 products are being evaluated now in clinical research studies, most in small phase I safety and acceptability trials. Furthest along in the development pipeline, either because they are already in phase II/IIb (expanded safety) or phase III (effectiveness) trials, or are anticipated to enter field trials in 2004 are Carraguard, Pro2000, Buffergel, C31G/Savvy, Dextrin-2-Sulfate/Emmelle and Cellulose sulfate.…”