Microemulsion-based media as novel drug delivery systems

https://onlinelibrary.wiley.com/doi/pdf/10.1021/js980403l

Solid dispersion of poorly water‐soluble drugs: Early promises, subsequent problems, and recent breakthroughs

Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each case, the theoretical basis for utility is described along with a detailed review of recent advances in the field. The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology (e.g., solid dispersions, lipid-based formulations, or salt forms) where required.

Strategies to Address Low Drug Solubility in Discovery and Development

Influence of microemulsions on cutaneous drug delivery.

ol triricinoleate 35) and polysorbate 80 (Tween 80; polyoxyethylene-sorbitan-20-monooleate) are widely used as drug formulation vehicles, including for the taxane anticancer agents paclitaxel and docetaxel. A wealth of recent experimental data has indicated that both solubilisers are biologically and pharmacologically active compounds, and their use as drug formulation vehicles has been implicated in clinically important adverse effects, including acute hypersensitivity reactions and peripheral neuropathy. CrEL and Tween 80 have also been demonstrated to influence the disposition of solubilised drugs that are administered intravenously. The overall resulting effect is a highly increased systemic drug exposure and a simultaneously decreased clearance, leading to alteration in the pharmacodynamic characteristics of the solubilised drug. Kinetic experiments revealed that this effect is primarily caused by reduced cellular uptake of the drug from large spherical micellar-like structures with a highly hydrophobic interior, which act as the principal carrier of circulating drug. Within the central blood compartment, this results in a profound

Pharmacological effects of formulation vehicles : implications for cancer chemotherapy.

Studies on microemulsions using Brij 96 as surfactant and glycerin, ethylene glycol and propylene glycol as cosurfactants

The present invention comprises a tablet, and method for making such, which disintegrates or dissolves in a matter of just a few seconds once placed into the oral cavity. Generally, the method of the present invention comprises up to four steps. First, a porous particulate powder which will serve as the tablet support matrix is produced. In the second step, the pharmaceutical, for example an antihistamine, decongestant, or antibiotic is combined with the powder. Other additives may also be added to the mixture. In the third step the mixture is formed into a tablet. Finally, in the fourth step, a coating may be applied to the outer surface of the tablet to enhance the intactness and durability of the tablet.

Method of making a rapidly dissolving tablet

The present invention comprises a particulate support matrix for making a tablet, and method for making such, which disintegrates or dissolves in a matter of just a few seconds once placed into the oral cavity. Thee particulate support matrix comprises a first polymeric component which may be a polypeptide, preferably a non-hydrolyzed gelatin, a second polymeric component which may be a different polypeptide which may be a hydrolyzed gelatin and a bulking agent. The porous particulate powder can serve as the tablet support matrix, to which a pharmaceutical, for example an antihistamine, decongestant, or antibiotic is added.

Process for making a particulate support matrix for making a rapidly dissolving tablet

Dissolution rates of corticosteroids utilizing sugar glass dispersions

A particulate support matrix, and a dosage form made therefrom, and processes for making such support matrices and dosage forms, which disintegrate or dissolve in a matter of just a few seconds once placed into an aqueous environment. First, a porous particulate powder matrix comprising at least two polymeric components which will serve as the dosage form matrix is produced. The polymeric components have different solubilities. In a second step, a pharmaceutical compound, for example an antihistamine, decongestant, or antibiotic is combined with the powder. Other additives may also be added to the mixture. In a third step the mixture is formed into a dosage form. Finally, in a fourth step, a coating may be formed upon the outer surface of the dosage form to enhance the intactness and durability of the dosage form.

Loyd V. Allen

Papers

Studies on microemulsions using Brij 96 as surfactant and glycerin, ethylene glycol and propylene glycol as cosurfactants

Method of making a rapidly dissolving tablet

Process for making a particulate support matrix for making a rapidly dissolving tablet

Dissolution rates of corticosteroids utilizing sugar glass dispersions

Rapidly dissolving dosage form