Recent Advances in the Excipients Used in Modified Release Vaginal Formulations

The formulation of an ideal vaginal drug delivery system (DDS), with the requisite properties, with respect to safety, efficacy, patient compliance, aesthetics, harmonization with the regulatory requirements, and cost, requires a meticulous selection of the active ingredients and the excipients used. Novel excipients defined by diversity and multifunctionality are used in order to ameliorate drug delivery attributes. Synthetic and natural polymers are broadly used in pharmaceutical vaginal formulations (solid, semi-solid dosage forms, implantable devices, and nanomedicines) with a promising perspective in improving stability and compatibility issues when administered topically or systemically. Moreover, the use of biopolymers is aiming towards formulating novel bioactive, biocompatible, and biodegradable DDSs with a controllable drug release rate. Overviewing vaginal microenvironment, which is described by variable and perplexed features, a perceptive choice of excipients is essential. This review summarizes the recent advances on the excipients used in modified vaginal drug delivery formulations, in an attempt to aid the formulation scientist in selecting the optimal excipients for the preparation of vaginal products.

REVIEW ON FORMULATION AND EVALUATION OF SOLID LIPID NANOPARTICLES FOR VAGINAL APPLICATION

Vaginal drug administration can improve prophylaxis and treatment of many conditions affecting the female reproductive tract, which includes fungal and bacterial infections, sexually transmitted diseases and cancer also. This is the best route for the administration of proteins, peptides, and also other therapeutic drugs like macro-molecules. For the administration of drugs like contraceptives, steroids, metronidazole, anti-retroviral, vaginal drug delivery is the most preferable route. However, achieving sufficient drug concentration in the vagina can be challenging because of its low permeability. The benefits of the vaginal drug delivery system are it increases the bioavailability, least systemic side effects; easiness of use and self-medication is possible. However vaginal drug delivery system is considered as a less effective route because of the unfortunate absorption of drugs across the vaginal epithelium. The traditional commercial preparations, such as creams, foams, gels, irrigations and tablets, are known to reside in the vaginal cavity for a relatively short period of time owing to the self-cleaning action of the vaginal tract and often require multiple daily doses to ensure the desired therapeutic effect. With the rapidly developing field of nanotechnology, the use of specifically designed carrier systems such as Nanoparticle-based drug delivery has been proven an excellent choice for vaginal application to overcome the challenges associated with the low permeability.

Vaginal Mucoadhesive Drug Delivery System

Mucoadhesive drug delivery systems are delivery systems which utilize the property of bioadhesion of certain polymers which become adhesive on hydration and hence can be used for targeting a drug to a particular region of the body for extended periods of time. Many of these delivery routes, particularly those through the nasal, ocular, reproductive and gastrointestinal system, involve contact with mucosal surfaces. The gastrointestinal route has been particularly popular among medical staff and patients alike. Although convenient, unfortunately, this route can be very inefficient for a number of reasons, including too rapid transit of the drug-containing delivery system past the optimum site for absorption, which is normally the small intestine and to a lesser degree the stomach and colon. Mucoadhesive formulations use polymers as the adhesive component. Mucoadhesive drug delivery systems are available in the form of tablets, films, patches, and gels for oral, buccal, nasal, ocular, vaginal, rectal and topical routes for both systemic and local effects. This review article represents the various aspects of vaginal drug delivery system, bioadhesion mechanism, Theory of bioadhesion, factors affecting bioadhesion, various types of vaginal formulation etc.

Manufacturing and Examination of Vaginal Drug Delivery System by FDM 3D Printing

Vaginal drug delivery systems can provide a long-term and constant liberation of the active pharmaceutical ingredient even for months. For our experiment, FDM 3D printing was used to manufacture the vaginal ring samples from thermoplastic polyurethane filament, which enables fast manufacturing of complex, personalized medications. 3D printing can be an excellent alternative instead of industrial manufacturing, which is complicated and time-consuming. In our work, the 3D printed vaginal rings were filled manually with jellified metronidazole or chloramphenicol for the treatment of bacterial vaginosis. The need for manual filling was certified by the thermogravimetric and heatflow assay results. The manufactured samples were analyzed by an Erweka USP type II Dissolution Apparatus, and the dissolution profile can be distinguished based on the applied jellifying agents and the API’s. All samples were considered non-similar based on the pairwise comparison. The biocompatibility properties were determined by prolonged MTT assay on HeLa cells, and the polymer could be considered non-toxic. Based on the microbiological assay on E. coli metronidazole and chitosan containing samples had bactericidal effects while just metronidazole or just chitosan containing samples bacteriostatic effect. None of these samples showed a fungistatic or fungicide effect against C. albicans. Based on our results, we successfully manufactured 3D printed vaginal rings filled with jellified metronidazole.

Recent Advances in Polymer-Based Vaginal Drug Delivery Systems

The vagina has been considered a potential drug administration route for centuries. Most of the currently marketed and investigated vaginal formulations are composed with the use of natural or synthetic polymers having different functions in the product. The vaginal route is usually investigated as an administration site for topically acting active ingredients; however, the anatomical and physiological features of the vagina make it suitable also for drug systemic absorption. In this review, the most important natural and synthetic polymers used in vaginal products are summarized and described, with special attention paid to the properties important in terms of vaginal application. Moreover, the current knowledge on the commonly applied and innovative dosage forms designed for vaginal administration was presented. The aim of this work was to highlight the most recent research directions and indicate challenges related to vaginal drug administrations. As revealed in the literature overview, intravaginal products still gain enormous scientific attention, and novel polymers and formulations are still explored. However, there are research areas that require more extensive studies in order to provide the safety of novel vaginal products.

Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

An optimal host–microbiota interaction in the human vagina governs the reproductive health status of a woman. The marked depletion in the beneficial Lactobacillus sp. increases the risk of infection with sexually transmitted pathogens, resulting in gynaecological issues. Vaginal infections that are becoming increasingly prevalent, especially among women of reproductive age, require an effective concentration of antimicrobial drugs at the infectious sites for complete disease eradication. Thus, topical treatment is recommended as it allows direct therapeutic action, reduced drug doses and side effects, and self-insertion. However, the alterations in the physiological conditions of the vagina affect the effectiveness of vaginal drug delivery considerably. Conventional vaginal dosage forms are often linked to low retention time in the vagina and discomfort which significantly reduces patient compliance. The lack of optimal prevention and treatment approaches have contributed to the unacceptably high rate of recurrence for vaginal diseases. To combat these limitations, several novel approaches including nano-systems, mucoadhesive polymeric systems, and stimuli-responsive systems have been developed in recent years. This review discusses and summarises the recent research progress of these novel approaches for vaginal drug delivery against various vaginal diseases. An overview of the concept and challenges of vaginal infections, anatomy and physiology of the vagina, and barriers to vaginal drug delivery are also addressed.