Application of Sol–Gels for Treatment of Gynaecological Conditions—Physiological Perspectives and Emerging Concepts in Intravaginal Drug Delivery (original) (raw)
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A Detailed Review on Novel Vaginal Drug Delivery Systems
2022
Traditional vaginal medication delivery methods include drawbacks such low bioadhesive characteristics, generate leakages, limited residence time in the genitourinary tract, and the vaginal tract's ability to self-clean itself. The creation of novel vaginal formulation technology is required to meet requirements such desired product dispersion throughout the vagina, retention for intended intervals, sufficient release of medications, and improvement of human reproductive health. The conventional medication delivery methods, such as pessaries, pills, creams, foams, irrigations, etc., are being replaced by the new vaginal drug administration systems as a result of advancements in pharmaceutical technology. Innovative drug-loaded inserts, hydro-gel systems containing phase change polymers like poloxamer exhibit sol-gel transition in response to body temperature, pH, and specific ions, liposomes, micro emulsion-based vaginal gel, vaginal rings, cubic gels, formulations based on polystyrene, and formulations based on silicone elastomers are some of the approaches used to develop recent vaginal drug delivery systems. The distribution of nanoparticulate drugs via the vaginal channel has become a new research trend. Unlike traditional methods of contraception and vaginal infections, novel approaches use applications other than those mentioned above. Vaginal delivery techniques have the potential to be utilised on a much larger scale than currently possible.
Novel Concepts In Vaginal Drug Delivery
The traditional vaginal drug delivery systems have limitations like poor bioadhesive properties; produce leakages, short residence time in the genitourinary tract and self-cleansing action of the vaginal tract. There is a need for the development of innovative vaginal formulation technology that fulfils certain criteria such as desirable product dispersion throughout the vagina, retention for intended intervals, and adequate release of drug and improvement of human reproductive health. With the advancement in pharmaceutical technology, the new vaginal drug delivery systems are taking the place of the traditional delivery systems such as pessaries, tablets, creams, foams, irrigations etc. Approaches used for the development of recent Vaginal Drug Delivery Systems include novel drug loaded inserts, hydro gel systems containing phase change polymers such as poloxamer exhibit sol–gel transition in response to body temperature, pH and specific ions, mucoadhesive drug delivery systems, liposome’s, micro emulsion based vaginal gel, vaginal rings, cubic gels, formulations based on polystyrene and formulations based on silicone elastomers. The recent trend of research work is on nanoparticulate drug delivery through vaginal route. Novel approaches use applications other than the conventional contraception and vaginal infections, this delivery system can be used to treat cancer and to deliver various proteinaceous and peptide drugs. The potential exists for a much wider use of vaginal delivery systems than currently existing systems.
Strategies to prolong the intravaginal residence time of drug delivery systems
Journal of Pharmacy and Pharmaceutical Sciences
The vagina has been studied as a favorable site for local and systemic delivery of drugs for female-related conditions. There are a large number of vaginal medications on the market and most of them require frequent application due to their short vaginal residence time. A prolonged vaginal residence time of formulations is therefore a key parameter for improved therapeutic efficacy. Promising approaches to prolong the residence time base on mucoadhesion, in- situ sol-gel transition and mechanical fixation. Mucoadhesive drug delivery systems can be tailored to adhere to the vaginal tissue. In-situ gelling systems offer the advantage of increased viscosity in vaginal cavity and consequently reduce outflow from the vagina. Mechanical fixation needs specially shaped drug delivery systems and reduce the frequency of administration significantly. Within this review an overview on these different strategies and systems is provided. Furthermore, the techniques to evaluate the potential of t...
Liposomal gels for vaginal drug delivery
International Journal of Pharmaceutics, 2001
The aim of our study was to develop a liposomal drug carrier system, able to provide sustained and controlled release of appropriate drug for local vaginal therapy. To optimise the preparation of liposomes with regards to size and entrapment efficiency, liposomes containing calcein were prepared by five different methods. Two optimal liposomal preparations (proliposomes and polyol dilution liposomes) were tested for their in vitro stability in media that simulate human vaginal conditions (buffer, pH 4.5). To be closer to in vivo application of liposomes and to achieve further improvement of their stability, liposomes were incorporated in vehicles suitable for vaginal self-administration. Gels of polyacrylate were chosen as vehicles for liposomal preparations. Due to their hydrophilic nature and bioadhesive properties, it was possible to achieve an adequate pH value corresponding to physiological conditions as well as desirable viscosity. In vitro release studies of liposomes incorporated in these gels (Carbopol 974P NF or Carbopol 980 NF) confirmed their applicability as a novel drug carrier system in vaginal delivery. Regardless of the gel used, even 24 h after the incubation of liposomal gel in the buffer pH 4.5 more than 80% of the originally entrapped substance was still retained.
Biomacromolecules, 2009
This investigation describes the formulation and characterization of rheologically structured vehicles (RSVs) designed for improved drug delivery to the vagina. Interactive, multicomponent, polymeric platforms were manufactured containing hydroxyethylcellulose (HEC, 5% w/w) polyvinylpyrrolidone (PVP, 4% w/w), Pluronic (PL, 0 or 10% w/w), and either polycarbophil (PC, 3% w/w) or poly(methylvinylether-co-maleic anhydride) (Gantrez S97, 3% w/w) as a mucoadhesive agent. The rheological (torsional and dynamic), mechanical (compressional), and mucoadhesive properties were characterized and shown to be dependent upon the mucoadhesive agent used and the inclusion/exclusion of PL. The dynamic rheological properties of the gel platforms were also assessed following dilution with simulated vaginal fluid (to mimic in vivo dilution). RSVs containing PC were more rheologically structured than comparator formulations containing GAN. This trend was also reflected in formulation hardness, compressibility, consistency, and syringeability. Moreover, formulations containing PL (10% w/w) were more rheologically structured than formulations devoid of PL. Dilution with simulated vaginal fluids significantly decreased rheological structure, although RSVs still retained a highly elastic structure (G′ > G′′ and tan δ < 1). Furthermore, RSVs exhibited sustained drug release properties that were shown to be dependent upon their rheological structure. It is considered that these semisolid drug delivery systems may be useful as siteretentive platforms for the sustained delivery of therapeutic agents to the vagina.
A Review on Vaginal Route as a Systemic Drug Delivery
Exhaustive efforts have been made to the administration of drugs, via alternative routes, that are poorly absorbed after the oral administration. The vaginal route of drug delivery has been known since ancient times. In recent years, the vaginal route has been rediscovered as a potential route for systemic delivery of peptides and other therapeutically important macromolecules. However, successful delivery of drugs through the vagina remains a challenge, primarily due to the poor absorption across the vaginal epithelium. The rate and extent of drug absorption after intra vaginal administration may vary depending on formulation factors, vaginal physiology, age of the patient and menstrual cycle. Suppositories, creams, gels, tablets and vaginal rings are commonly used vaginal drug delivery systems. The purpose of this communication is to provide the reader with a summary of advances made in the field of vaginal drug delivery. This report, therefore, summarizes various vaginal drug delivery systems and factors affecting drug absorption from the vaginal route. The objective of this paper is to provide an overview of various vaginal drug delivery systems currently in development stages are available in the market, immunization via the vagina and special emphasis on the challenges and difficulties associated with systemic delivery of drugs via the vaginal route.
In vivo evaluation of an in-situ hydrogel system for vaginal administration
The vaginal retention and local irritation of a carrageenan, poloxamer 407 and carbopol-based thermosensitive hydrogel system for vaginal drug delivery was assessed. Results showed that the residence of hydrogel in the mouse vagina following intravaginal administration was prolonged by carrageenan and further prolonged by the addition of a mucoadhesive component (carbopol). The optimal hydrogel formulation was proven to be safe for vaginal use in rabbits.
Recent Advances in Polymer-Based Vaginal Drug Delivery Systems
Pharmaceutics, 2021
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 ov...
The vaginal mucosa is a very promising route for drug administration due to its high permeability and the possibility to bypass first pass metabolism; however, current vaginal dosage forms present low retention times due to their dilution in vaginal fluids, which hampers the efficacy of many pharmacological treatments. In order to overcome these problems, this study proposes to develop a mucoadhesive in situ gelling liquid crystalline precursor system composed of 30% of oleic acid and cholesterol (7:1), 40% of ethoxylated and propoxylated cetyl alcohol, and 30% of a dispersion of 16% Poloxamer 407. The effect of the dilution with simulated vaginal fluid (SVF) on this system was evaluated by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheological studies, texture profile analysis (TPA), mucoadhesion study, in vitro drug release test using hypericin (HYP) as drug model, and cytotoxicity assay. PLM and SAXS confirmed the formation of an isotropic system. After the addition of three different concentrations of SVF (30, 50, and 100%), the resultant formulations presented anisotropy and characteristics of viscous lamellar phases. Rheology shows that formulations with SVF behaved as a non-Newtonian fluid with suitable shear thinning for vaginal application. TPA and mucoadhesion assays indicated the formation of long-range ordered systems as the amount of SVF increases which may assist in the fixation of the formulation on the vaginal mucosa. The formulations were able to control about 75% of the released HYP demonstrating a sustained release profile. Finally, all formulations acted as safe vaginal drug delivery systems.
Development of mucoadhesive adapalene gel for biotherapeutic delivery to vaginal tissue
Frontiers in Pharmacology, 2022
Purpose: Alternate formulation strategies need to be devised for improving the absorption and bioavailability of drug molecules administered through the intravaginal route. Enhancing the coating of vaginal mucosa can aid the achievement of this goal. The aim of the current study is to develop a mucoadhesive formulation having adequate adhesiveness, spreading, and viscosity profiles that can ensure good tissue absorption of adapalene upon intravaginal application. Method: A combination of mucoadhesive agents has been employed, including Carbopol-934, HPMC K-15M, and xanthan gum, in varying ratios to formulate five different gels. Furthermore, a cost-effective UV-spectroscopic analytical method was developed to quantify the amount of adapalene in tested samples, both of in vitro and in vivo origin. The analytical method was validated for different parameters, including specificity, linearity, range, accuracy, precision, and ruggedness. The modified USP-II apparatus was used for dissolution studies, while in vivo pharmacokinetic validation was performed in a murine model. Result: Of all the tested formulations, on the basis of the rheo-mechanical attributes, ACX3 performed better than the rest, including the commercially available intravaginal reference product. ACX3 had an average adhesion time of 12 min and a spread diameter of 37 mm. It showed 35 mm as average distance travelled by the diluted sample for leakage assessment. The analytical method developed for the adapalene muco-adhesive gel was within the range for all the validation parameters. For further evaluating the performance of the formulation, dissolution studies were conducted in simulated vaginal conditions which showed 94.83% of drug release within 5 minutes, while on completion of 30 min, it was measured to be 92.90%. Moreover, approximately 67% of the administered drug was recovered after 5 min of administration as evaluated through tissue recovery procedures in mice.