María-Dolores Veiga

Chitosan and Kappa-Carrageenan Vaginal Acyclovir Formulations for Prevention of Genital Herpes. In Vitro and Ex Vivo Evaluation.

Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Polysaccharides, such as chitosan and carrageenan, which have good binding capacity with mucosal tissues, are now included in vaginal delivery systems. Marine polymer-based vaginal mucoadhesive solid formulations have been developed for the controlled release of acyclovir, which may prevent the sexual transmission of the herpes simplex virus. Drug release studies were carried out in two media: simulated vaginal fluid and simulated vaginal fluid/simulated seminal fluid mixture. The bioadhesive capacity and permanence time of the bioadhesion, the prepared compacts, and compacted granules were determined ex vivo using bovine vaginal mucosa as substrate. Swelling processes were quantified to confirm the release data. Biocompatibility was evaluated through in vitro cellular toxicity assays, and the results showed that acyclovir and the rest of the materials had no cytotoxicity at the maximum concentration tested. The mixture of hydroxyl-propyl-methyl-cellulose with chitosan- or kappa-carrageenan-originated mucoadhesive systems that presented a complete and sustained release of acyclovir for a period of 8–9 days in both media. Swelling data revealed the formation of optimal mixed chitosan/hydroxyl-propyl-methyl-cellulose gels which could be appropriated for the prevention of sexual transmission of HSV.

Study of Surfactants/β-Cyclodextrin Interactions Over Mequitazine Dissolution

AbstractSurfactant/β-cyclodextrin interactions were investigated by studying the dissolution of mequitazine in different binary (aqueous solutions of β-CD or surfactants) and ternary (aqueous solution of β-CD and surfactants) dissolution media. Results were compared with those obtained from binary media with 50, 250, and 500 mg of surfactants (preceding paper). Results show that there is an interaction between β-cyclodextrin and surface-active agent, and that the type and extent of interaction are controlled by the nature and the amount of the surface-active agent. A decrement in drug dissolution rate was obtained from all of the ternaly media containing β-cyclodextrin and sodium lauryl sulfate as surfactant in the ratio of 1:1 mol/mol. These facts suggest that sodium lauryl sulfate and β-cyclodextrin form an inclusion compound in the molecular ratio of 1:1.

Drug kinetics release from Eudragit – Tenofovir@SiOC tablets

A novel drug release system has been obtained in form of tablets from Eudragit® RS and tenofovir loaded on porous silicon oxycarbide glasses (SiOC). Active carbon (AC) and mesoporous silica (MCM-41) have also been used for comparative purposes. The porous silicon oxycarbide presents a bimodal mesopore size distribution that is maintained after functionalization with amino groups. We have studied the adsorption kinetics and adsorption equilibrium when the materials are loaded with tenofovir and, in all cases, pseudo-second order kinetics and Langmuir isotherm have been revealed as the most representative models describing the kinetic and thermodynamic parameters. Besides, the tenofovir adsorption on these materials turns out to be a favorable process. In vitro release of tenofovir has been studied in simulated vaginal medium by applying different release models. Continuous tenofovir release for >20days has been obtained for the SiOC material functionalized with amine groups. We concluded that the drug release occurs in two steps that involve a drug diffusion step through the material pores and diffusion through the swollen polymer. The interactions between the tenofovir drug and de amine groups of the functionalized silicon oxycarbide also play an important role in the release process.

Optimization of tenofovir release from mucoadhesive vaginal tablets by polymer combination to prevent sexual transmission of HIV

The use of sustained-release mucoadhesive vaginal tablets of antiretroviral drugs as microbicidal formulations can be an effective strategy for reducing the sexual transmission of HIV from men to women, which is a main problem particularly in low- and middle-income countries. Different polymers (hydroxypropylmethyl cellulose (HPMC), chitosan, guar gum and Eudragit® RS) have proven some good features for this purpose. At this work, these polymers have been combined in pairs in different proportions to enhance the advantages offered by each one individually. The in vitro release of tenofovir from the matrices, ex vivo mucoadhesive capacity (evaluated on vaginal mucosa) and the degree of swelling in simulated vaginal fluid have been assessed. A multimodal pore size distribution is observed in porosimetry studies -carried out with swelling witnesses-, due to the contribution of polymers with different swelling behaviour to the pore formation, and it is corroborated by scanning electron microscopy. X-ray diffraction technique confirms the changes in crystallinity of the formulation after swelling. We can report that the combination of HPMC and chitosan in the same formulation may be useful for the prevention of sexual transmission of HIV, since tablets can be obtained that remain adhered to the vaginal mucosa for 96h, so the drug is released in a sustained manner for 72h. When the formulation contains more chitosan than HPMC the swelling is moderate, making it more comfortable for women to apply.

Hydroxypropyl Gamma Cyclodextrin as a Solubiliser and Dissolution Enhancing Agent: The Case of Tolbutamide—A Poorly Water-Soluble Drug

Hydroxypropyl cyclodextrins are one of the most freely soluble cyclodextrin derivatives. These cyclodextrins have been found very useful in parenteral preparations [1] and in solid dosage forms [2] because of their non-toxic nature, complete and rapid dissolution in water. Hydroxypropyl gamma cyclodextrin can effectively encapsulate a number of bulky drug molecules due to its large cavity diameter. Tolbutamide is a poorly water-soluble hypoglycaemic agent; it forms inclusion compounds with b-cyclodextrin [3,4] and hydroxypropyl b-cyclodextrin [5]. In this paper attempt has been made to know if the solubility and dissolution of this drug become affected due to the presence of hydroxypropyl gamma cyclodextrin both in kneaded systems and in physical mixtures.

Improvement of Tenofovir vaginal release from hydrophilic matrices through drug granulation with hydrophobic polymers

&NA; Sustained‐release vaginal microbicides hold out great hope for the prevention of sexual transmission of HIV from men to women. Tenofovir (TFV) –an antiretroviral drug– sustained‐release vaginal compacts combining two release control systems (by drug‐loading granules with hydrophobic polymers and incorporating them in a hydrophilic matrix) are proposed in this work as a possible microbicide. The polymers used for the drug granules are Eudragit® RS (ERS), an acrylic derivative, and Zein, a maize protein. The hydrophilic matrix is composed of a mixture of hydroxypropylmethyl cellulose (HPMC) and chitosan (CH). The thermal, microscopic, spectrophotometric and X‐ray diffraction analysis showed that the drug was not altered during the granulation process. Studies of TFV release, swelling and ex vivo mucoadhesion were subsequently performed on simulated vaginal fluid. The formulation whereby TFV is granulated using twice its weight in ERS, and then including these granules in a matrix in which the CH predominates over HPMC, allows the sustained release of TFV for 144 h, mucoadhesion to the vaginal mucosa for 150 h and a moderate swelling, making it the most suitable formulation of all those studied. These compacts would therefore offer women protection against the sexual acquisition of HIV. Graphical abstract Figure. No caption available.

Influence of Surfactants over the Dissolution of Mequitazine

AbstractInfluence of surfactants over the dissolution of mequitazine was investigated by studying the dissolution of mequitazine (a poorly water-soluble drug) in different binary media prepared by adding different amounts of surfactants (Brij 35, Tween 20 or sodium lauryl sulfate (SLS)) into 1 liter of water. An improvement in drug dissolution rate was observed from all of the binary dissolution media, except those containing lower amounts of sodium lauryl sulfate. At lower concentrations, SLS acts as a true salt, and a competition is produced between drug and SLS for water molecules. Due to this saline effect, a decline in drug dissolution was observed from binary media with lower concentration of SLS

Characterization and Dissolution Study of Oxodipine from Solid Binary Systems

AbstractThennomicroscopy and differential scanning calorimetry were employed to characterize solid binary systems prepared with oxodipine and PEG 6000, 2-hydroxypropyl-β-cyclodextrin or mannitol. DSC curves did not allow to diferentiate physical mixtures from solid dispersions. Thennomicroscopy revealed the interactions that can be produced between drug and each carrier, due to heat contribution, when the physical mixtures were observed; also this thermal technique permited us to ascertain the composition of particles that constitute the solid dispersions. Dissolution studies showed that the amelioration obtained in oxodipine dissolution from physical mixtures was due to the dessagregant action of the carriers, which obtained an increase of the drug surface in contact with the dissolution medium. The proportions and carrier nature influence the oxodipine dissolution, fundamentally from solid dispersions, where the interaction drug/carrier is stronger than in physical mixtures.

Polymer Gels in Vaginal Drug Delivery Systems

Vaginal drug delivery is a promising route for the treatment and prevention of local and systemic diseases such as genital herpes or AIDS. Suitable excipients must be selected to optimize the residence time of formulations in vaginal mucosa and could be included in the formulation. Many polymers are excellent choices for the development of vaginal drug delivery systems due to their properties of mucoadhesion, biocompatibility and biodegradability. These polymers swell in the aqueous medium of the vaginal environment and generate a gel layer which allows controlled release of the drug. The thickness and viscosity of the gel layer determine the drug release process. The aim of this chapter is to review the different polymers available for the development of vaginal delivery systems and to describe their physicochemical (swelling, viscosity, mucoadhesion), biopharmaceutical (drug release, biodegradability) and cytotoxic properties.

Hydrogels: Biomedical uses

Abstract Hydrogels have been widely exploited for biomedical uses due to their rheological and physical properties, their biocompatibility, and their ability to control the release of drugs. Recent developments in nanotechnology applied to hydrogels have taken them one step further, resulting in the production of nanogels. Several polymers and methods have been assessed for use in manufacturing nanogels and for loading with different drugs. These nanocarriers have proved to be versatile tools for therapy thanks to their various properties and the fact that they can be oriented to be stimuli sensitive. These possibilities make them useful for drug delivery systems, as they can target a specific organ and release the drug in a sustained manner.