Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics
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.
Solid-Lipid Nanoparticles
Examples of various drugs developed by SLN technology
Drug | Lipid Utilized | Biopharmaceutical Application |
---|---|---|
5-Fluoro uracil | Dynasan 114 and Dynasan 118 | Prolonged release in simulated colonic media |
Ibuprofen | Stearic acid, triluarin and tripalmitin | Stable formulation with low toxicity |
Apomorphine | Glycerylmonostearate, polyethylene glycol monostearate | Enhanced bioavailability in rats |
Idarubicin | Emulsifying wax | Delivery of oral proteins |
Calcitonin | Trimyristin | Improvement of the efficacy of proteins |
Lopinavir | Compritol 888 ATO | Bioavailability enhanced |
Clozapine | Trimyristin, tristearin and tripalmitin | Improvement of bioavailability |
Nimesulide | Glycerylbehanate, glyceryltristearate, palmitostearate | Sustained release of the drug |
Cyclosporin A | Glycerylmonostearate and glycerylpalmitostearate | Controlled release |
Progesterone | Monostearin, oleic acid and stearic acid | Potential for oral drug delivery |
Gonadotropin release hormone | Monostearin | Prolonged release |
Repaglinide | Glycerylmonostearate and tri stearin | Reduced toxicity |
Lipid excipients are frequently used in lipid-based nanocarriers
Excipient | Chemical | Type of Carrier | Comments | References |
---|---|---|---|---|
Soybean oil | Triglycerides (longchain) | Nanoemulsions | Liquid, good biocompatibility, minimal physiological impact, weak solubilizing capacity | [125–127] |
Olive oil | Triglycerides (long-chain) | Nanoemulsions | Liquid, healthy, high monounsaturated fatty acids, and simple to emulsify | [126,128–131] |
Hemp oil | Medium/long-chain triglycerides blended with low-molecular weight lipids | Nanoemulsions | The liquid contains tocopherols, tocotrienols, phyrosterols, phospholipids, and other important fatty acids, good hydrophilicity, and self-emulsifiability. | [132,133] |
Caprylic/capric triglycerides | Triglycerides (medium-chain) | Nanoemulsions | Liquid, solubilizing capacity, compatible with other lipids, easy to emulsify. | [134–139] |
Captex® Series | Triglycerides (medium-chain) | Nanoemulsions | Liquid, fine solubilizing and emulsifying capacities, miscible with other lipids | [140–142] |
Capmul MCM | Mono/diglycerides (medium-chain) | Nanoemulsions | Liquid, an excellent solvent powder for many organic compounds, can use as an emulsifier. | [143–146] |
Capmul MCM C8 | Glycerol monocaprylate Nanoemulsions | Nanoemulsions | Liquids, property similar to that of Capmul MCM. | [147–149] |
MaisineTM 35-1 | Glycerol monolinoleate | SEDDS | Liquid, solubilizer, bioavailability enhancer, oil phase in SEDDS | [150–153] |
PeceolTM | Glyceryl monolete | SEDDS; NLCs; Cubosomes | Liquid, lipid dispersion agent, oil-soluble surfactant, moisturizer | [154–156] |
Lauroglycol® 90 | Propylene glycol monolaurate | Nanoemulsions; SEDDS; NLCs | Liquid, water-insoluble surfactant of SEDDS, solubilizer, bioavailability enhancer, skin penetration solubilizer enhancer. | [157–159] |
Download the full review as PDF here Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics
or read it here
Bhalani, D.V.; Nutan, B.; Kumar, A.; Singh Chandel, A.K. Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics. Biomedicines 2022, 10, 2055. https://doi.org/10.3390/biomedicines10092055