Polymeric gels for intravaginal drug delivery

Abstract

Intravaginal drug delivery can elicit a local effect, or deliver drugs systemically without hepatic first pass metabolism. There are a number of emerging areas in intravaginal drug delivery, but the vagina is a challenging route of administration, due to the clearance mechanisms present which result in poor retention of dosage forms, and the potential for irritation and other adverse reactions. Gel formulations are desirable due to the ease of application, spreading and that they cause little to no discomfort to the patient. However, these dosage forms, in particular, are poorly retained and traditional gels typically have little control over drug release rates. This has led to a large number of studies on improving the retention of vaginal gels and modulating the controlled release of drugs from the gel matrix. This review outlines the anatomy and physiology of the vagina, focussing on areas relevant to drug delivery. Medical applications of vaginally administered medicines is then discussed, followed by an overview of polymeric gels in intravaginal drug delivery. The sensorial properties of intravaginal gels, and how these relate to user compliance are also summarised. Finally, some important barriers to marketing approval are described.

Pharmaceutical topical gel containing proanthocyanidin polymers-rich fraction from Stryphnodendron adstringens

“…The female genital tract can show pH from slightly basic to moderately acidic, and it is important that a topical formulation maintain its pH near physiological values to prevent discomfort in patients. Besides, the change of pH in a pharmaceutical formulation can show some degradation reactions, compounds interactions, microbial contamination, viscosity alteration and others (Cook and Brown, 2018). The TP content in TG was smaller than 5% during the storage time in both conditions.…”

Modifying the Properties of Thermogelling Poloxamer 407 Solutions through Covalent Modification and the Use of Polymer Additives

“…As the temperature increases, P407 unimers increasingly start to aggregate to form micelles because of the entropically driven desolvation of PPO blocks, accompanied by a reduction in the CMC . This causes the equilibrium to shift toward a larger volume fraction of micelles (Ø > 0.53), which in turn leads to micelle packing and transition from liquid solution to gel as shown in Figure . The size and aggregation number of the micelles are unchanged at the high concentrations and temperatures of the gel state, which has been determined to have a face‐centered cubic lattice by small‐angle neutron scattering and small‐angle X‐ray scattering.…”

“…Tgel is highly important for biomedical applications . For instance, if Tgel was lower than room temperature, there would be difficulty in the manufacture, handling, and application of a medicine.…”

“…Mucoadhesion describes the force with which a dosage form binds to a mucus membrane to avoid the formulation leaking from the mucosal surface . P407 solutions typically showed low mucoadhesion . The mucoadhesion may be calculated as the force required to separate the gel from ex vivo mucosal tissue, often measured with a texture analyzer .…”

“…Poloxamer 407, a poly(ethylene glycol)–poly(propylene glycol)–poly(ethylene glycol) triblock copolymer, is the most commonly used thermogelling material in published research. It is chemically stable, has been used as an excipient in licensed medicines, and is inexpensive . As such, it has been widely investigated for various biomedical applications, including drug delivery, wound dressings, and cell culture .…”