Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics

Abstract

The low water solubility of pharmacoactive molecules limits their pharmacological potential, but the solubility parameter cannot compromise, and so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, oral dosage forms cover more than 50%, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry’s screening programs identified that around 40% of new chemical entities (NCEs) face various difficulties at the formulation and development stages. These pharmaceuticals demonstrate less solubility and bioavailability. Enhancement of the bioavailability and solubility of drugs is a significant challenge in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibit poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of poorly water-soluble drugs, for example, the complexation of active molecules, the utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelle preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, the solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, the use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, referring to a number of appropriate research reports.

Application of Design of Experiments in the Development of Self-Microemulsifying Drug Delivery Systems

“…In addition, due to the difficulty in disintegrating and dissolving in the gastrointestinal tract, the bioavailability of poorly soluble drugs after oral administration is prone to be low. Physical and chemical modifications of poorly water-soluble drugs have been used to increase their solubility and bioavailability, but there are still some limitations [ 3 , 4 ]. For example, salt form and derivatization may alter the physiochemical properties; however, the change of pH in the physiological environment may lead to drug aggregation or precipitation [ 5 ].…”

Injectable leonurine nanocrystal-loaded microspheres for long-term hyperlipidemia management

“…Drug micronization can enhance the dissolution rate and bioavailability of poorly soluble drugs or facilitate formulation processing, which can be achieved by milling, high-pressure homogenization, spray drying, etc. 21,22 The scanning electron microscopy (SEM) images of the raw drug (Leo) exhibited an irregular crystalline shape with a size ranging from 50-300 μm (Fig. 1a).…”

A New Challenge for the Old Excipient Calcium Carbonate: To Improve the Dissolution Rate of Poorly Soluble Drugs

“…Thus, with of the aim of improving drug bioavailability and allowing new pharmaceutical entities to reach the market, many technological strategies have been investigated for improving dissolution rates and for solving problems related to poor solubility. Chemical techniques that have been employed are the formation of prodrugs and the use of different salts [ 3 , 4 , 5 ]. The main physical strategies are micronization, the use of polymorphic or amorphous forms and co-crystals, and the formulation strategies include solid dispersions, inclusion complexes and solid-liquid techniques [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ].…”

“…Chemical techniques that have been employed are the formation of prodrugs and the use of different salts [ 3 , 4 , 5 ]. The main physical strategies are micronization, the use of polymorphic or amorphous forms and co-crystals, and the formulation strategies include solid dispersions, inclusion complexes and solid-liquid techniques [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. The presence of excipients such as surfactants, polymers, super-disintegrants and multifunctional excipients can also accelerate drug release [ 10 , 11 ].…”