Kavita Vermani

Hydrogels: from controlled release to pH-responsive drug delivery

Hydrogels are one of the upcoming classes of polymer-based controlled-release drug delivery systems. Besides exhibiting swelling-controlled drug release, hydrogels also show stimuli-responsive changes in their structural network and hence, the drug release. Because of large variations in physiological pH at various body sites in normal as well as pathological conditions, pH-responsive polymeric networks have been extensively studied. This review highlights the use of hydrogels (a class of polymeric systems) in controlled drug delivery, and their application in stimuli-responsive, especially pH-responsive, drug release.

Herbal medicines for sexually transmitted diseases and AIDS

Sexually transmitted diseases (STDs) and acquired immunodeficiency syndrome (AIDS) are gaining significant importance at present due to rapid spread of the diseases, high cost of treatment, and the increased risk of transmission of other STDs and AIDS. Current therapies available for symptomatic treatment of STDs and AIDS are quite expensive beyond the reach of common man and are associated with emergence of drug resistance. Many patients of STDs and AIDS are seeking help from alternative systems of medicines such as Unani, Chinese, Ayurvedic, naturopathy, and homeopathy. Since a long time, medicinal plants have been used for the treatment of many infectious diseases without any scientific evidence. At present there is more emphasis on determining the scientific evidence and rationalization of the use of these preparations. Research is in progress to identify plants and their active principles possessing activity against sexually transmitted pathogens including human immunodeficiency virus (HIV) with an objective of providing an effective approach for prevention of transmission and treatment of these diseases. In the present review, plants reported to possess activity or used in traditional systems of medicine for prevention and treatment of STDs including AIDS, herbal formulations for vaginal application, and topical microbicides from herbal origin, have been discussed.

The scope and potential of vaginal drug delivery

The vagina, in addition to being a genital organ with functions related to conception, serves as a potential route for drug administration. Mainly used for local action in the cervico-vaginal region, it has the potential of delivering drugs for systemic effects and uterine targeting. Currently available vaginal dosage forms have several limitations, necessitating the need to develop novel drug delivery systems. In addition, consideration of the regulatory aspects and consumer preferences for vaginal formulations is also required in the early stages of development.

Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM) ☆

Vaginal prophylactic methodology may prevent heterosexual transmission of the HIV and other sexually transmitted disease-causing organisms as well as unplanned pregnancies. A new delivery system (ACIDFORM) was designed with acid-buffering, bioadhesive, and viscosity-retaining properties to (1) maintain the acidic vaginal milieu (the low pH inactivates many pathogens and spermatozoa), (2) form a protective layer over the vaginal/cervical epithelium (minimizing contact with pathogenic organisms), and (3) provide long-term vaginal retention. A Phase I clinical study with ACIDFORM provided initial information about its safety and showed the formation of a layer over the vaginal/cervical epithelium [1; Amaral et al., Contraception 1999;60:361-6]. To study the properties of the gel (without active ingredient) in more detail, ACIDFORMs acid-buffering, bioadhesive, viscosity-retaining, and spermicidal properties were compared in vitro to marketed formulations, and its long-term stability was assessed. ACIDFORM, either when titrated with NaOH or when mixed directly with semen, is highly acid buffering and much more effective than Aci-Jel, a commercial acid-buffering vaginal product. ACIDFORM adheres well to two model membranes (excised sheep vagina and cellophane) and is more bioadhesive than Conceptrol, Advantage S, Replens, Aci-Jel, and K-Y jelly. On dilution, ACIDFORM also retains its viscosity better than these marketed products. ACIDFORM is spermicidal and is stable for at least 2 years. These results suggest that ACIDFORM has advantages over presently marketed vaginal delivery systems. The gel may either be useful by itself as an antimicrobial contraceptive product or as a formulation vehicle for an active ingredient with antimicrobial and/or contraceptive properties.

Development and Characterization of Bioadhesive Vaginal Films of Sodium Polystyrene Sulfonate (PSS), a Novel Contraceptive Antimicrobial Agent

No HeadingPurpose.Polystyrene sulfonate (PSS) is a novel noncytotoxic antimicrobial contraceptive agent. A gel formulation of PSS was found safe for vaginal administration in phase I clinical trials. The purpose of the current study was to develop and evaluate novel bioadhesive vaginal film formulations of PSS.Methods.PSS films were prepared by solvent evaporation and optimized for various physical, mechanical, and aesthetic properties. Further, films were evaluated for various biological activities and safety.Results.Vaginal films containing 300 mg PSS per unit have been developed, using generally regarded as safe (GRAS) listed excipients. The films are colorless, transparent, thin, soft, and tough, dissolve rapidly in physiologic fluid to form a smooth, viscous and bioadhesive solution that could be retained in the vagina for prolonged intervals. Sperm function inhibition (hyaluronidase and cervical mucus penetration) and antimicrobial activities against human immunodeficiency virus (HIV) and herpes simplex virus (HSV) by PSS films were found comparable to PSS. Also, films did not inhibit normal vaginal microflora (Lactobacillus) and were noncytotoxic as indicated by negligible sperm immobilization and cytotoxicity to host cell assays.Conclusions.Rapidly dissolving bioadhesive vaginal film formulation of PSS with desired physical, mechanical, aesthetic, and biological properties is a suitable candidate vaginal microbicide for prevention of sexually transmitted disease (STDs) and is ready for toxicological and clinical evaluation.

Assemblies for In Vitro Measurement of Bioadhesive Strength and Retention Characteristics in Simulated Vaginal Environment

ABSTRACT The vaginal route of administration offers a promising option for local and systemic delivery of drugs. Conventional vaginal formulations are associated with limitations of poor retention, leakage, and messiness, thereby causing inconvenience to users. To overcome these limitations, formulations that adhere to the vaginal mucosa for a sufficient period of time need to be developed. Bioadhesion and retention are desirable characteristics of a vaginal formulation to achieve desired efficacy. These properties can be built in during formulation development by the use of bioadhesive polymers. In the present study, assemblies for in vitro measurement of bioadhesive strength and retention characteristics of vaginal formulations have been developed. A modified simulated vaginal fluid (SVFM) was used to simulate vaginal conditions for bioadhesion studies. Cellophane hydrated with SVFM and isolated sheep vaginal mucosa were used as model membranes. The bioadhesive potential of various polymers and their combinations was evaluated. Among the polymers evaluated, xanthan gum (XG), sodium alginate (SA), Polycarbophil (PC), and their combinations (XG + SA and XG + PC) were found to possess significant bioadhesive strength. In retention experiments, XG, SA, and combinations (XG + SA and XG + PC) were retained in isolated sheep vaginal tissue, while PC exhibited poor retention under experimental conditions. Based on the results of the study conducted, XG, SA, and combinations (XG + SA and XG + PC) have been proposed as potential candidates for developing bioadhesive vaginal drug delivery systems.

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

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.

Development of Novel Sustained Release Bioadhesive Vaginal Tablets of Povidone Iodine

Iodine has long been used as an antiseptic for the prevention and treatment of vaginal infections. The present study was aimed at the development of rapidly disintegrating, bioadhesive and sustained release vaginal tablets of an iodophore, polyvinylpyrrolidone (povidone iodine), their evaluation and comparison with the marketed formulations. The formulation development included drug-excipient compatibility studies, optimization of performance parameters like disintegration time, bioadhesion and drug release profile and comparison of physical properties and performance parameters with the marketed formulation. The developed formulation provided a sustained release of polymer complexed iodine (up to 8 hrs), rapid disintegration (< 1 min.), desired bioadhesive properties and retention for a prolonged time.

Survey of vaginal formulations available on the Indian market: physicochemical characterization of selected products

SummaryThe vagina is a potential site for the local and systemic delivery of drugs. Presently, significant attention is given to the development of vaginal formulations (‘microbicides’) that prevent sexual acquisition of acquired immunodeficiency syndrome (AIDS) and other sexually transmitted diseases. Acceptability of vaginal dosage forms may vary among women from different geographical and socioeconomic backgrounds. Therefore, in the drug development process, selection of an appropriate dosage form is crucial for consumer acceptance and use. The primary objective of this study was to survey vaginal preparations available in the Indian market to determine the types of products that are most frequently used by Indian women. In addition, this survey provides information about the active ingredients and dosage forms of these products. The physicochemical properties of selected products were compared in order to help formulation scientists to design vaginal formulations with desired properties. Indian vaginal products are available in several different dosage forms. Tablets are marketed most frequently (38%), followed by gels (15%) and creams (15%). The evaluated products varied greatly in their physicochemical properties such as colour, pH, disintegration, viscosity, osmotic pressure and bioadhesive properties. The information can serve as reference on vaginal products in the Indian market and to aid in the development of new vaginal formulations, especially for India and other tropical countries.