Solubility is supposed to be one of the most pivotal parameters for achieving an anticipated pharmacological response which requires sufficient concentration of drug in systemic circulation. Given the unpleasant fact that the majority of drug candidates (more than 75% of the total compounds being tested) are practically insoluble in water, the low aqueous solubility hence represents a major challenge for scientists to develop the formulation for many of chemical entities. Since low aqueous solubility of a compound often implies an undesirable bioavailability and finally severely limits its commercial viability, achieving the desired solubility is, therefore, becoming increasingly prevalent in drug pipelines across the industry.
Particle size, as a critical parameter which determines the solubility of a drug candidate, is strictly controlled during all stages of drug development. In general, reducing the particle size leads to an increase of surface area to volume ratio of the compound, which finally permits an efficient, reproducible, and economic means of solubility enhancement. Micronization or nanonization represents one of the most potential approaches to enhance the surface area and saturation solubility through the ways of reducing particle size to sub-micron level.
For those new chemical entities with very low solubility, no matter in the aqueous phase or oleic phase, undesirable plasma concentration is the main obstacle for achieving an ideal oral bioavailability. Nanosuspension or microsuspension has been recently regarded as one of the most efficient strategies to increase the dissolution rates and improve the bioavailability of many hydrophobic drug substances. Generally, a pharmaceutical nanosuspension or microsuspension is a biphasic system which is mainly composed of nano sized or micro sized drug particles.
Spray drying, one of the most popular and efficient methods for improving the solubility, involves dissolving the drug in an organic solvent in the presence of a polymer. Then the obtained solution is subjected to spray drying to form a dispersion which can be termed as a spray-dried dispersion or SDD. BOC Sciences has a highly proved capacity of developing and manufacturing SDDs to achieve a desirable oral bioavailability by overcoming poor drug solubility and delivery challenges.
As a technique commonly used in the polymer industry, hot melt extrusion (HME) is proven to be an efficient and economic technology for bioavailability enhancement of a wide range of hydrophobic drugs. Unlike other solubility enhancement strategies, HME is a combination of melting and mechanical energy that can improve continuous processing for reproducible analysis of materials, dust reduction and online monitoring.
Liquid-filled hard capsule (LFHC) represents an advanced alternative dosage form that is offered in both gelatin and hypromellose for liquid, semi-solid, paste and multiparticulate applications. LFHC has a great capability of addressing complex bioavailability challenges for those indissolvable APIs.
Lipid-based drug delivery systems (LBDDS) and complexes are becoming the increasingly important tools in the quest to improve the oral bioavailability of poorly soluble drugs. Unlike conventional tablets or powder-filled capsules, LBDDS can enhance the bioavailability of the drug compound by presenting the substances in a solubilized state and hence eliminating dissolution rate limited absorption.
At BOC Sciences, various techniques such as physical and chemical modifications of drug, particle size reduction, crystal engineering, salt formation, solid dispersion, use of surfactant, complexation and other methods will be applied to improve the solubility of your hydrophobic drugs. Our experts have extensive expertise in approaching many kind of drug substance solubility challenges especially the BCS II chemical entities. More importantly, the solubility enhancement technologies and methods will be identified and selected depends on drug property, site of absorption, and required dosage form characteristics, which helps eliminate rework and worry later on, saving you time and money.
References