Improving Bioavailability and Solubility of Poorly Soluble Drugs- A systematic review
Keywords:
N\AAbstract
Poor solubility is one of the primary reasons for the failure of new drug formulations to reach the market. In fact, a large proportion of new chemical entities (NCEs) exhibit poor water solubility, which limits their absorption and bioavailability. Bioavailability is the fraction of the administered dose of a drug that reaches the systemic circulation and is available at its site of action. Poor bioavailability can result from a variety of factors, including poor solubility, extensive first-pass metabolism, instability of the molecule in circulation and the properties of the drug molecule itself. Enhancing the solubility of poorly soluble drugs is, therefore, a major focus of pharmaceutical research, as it directly impacts their bioavailability and therapeutic efficacy. In this review we summarize the strategies and techniques used to improve the bioavailability and solubility of poorly soluble drug molecules and formulations. These include both physical and chemical modifications to drug formulations, as well as new technologies such as nanotechnology. By improving solubility, it is possible to enhance the drug's absorption, thereby increasing bioavailability. Various methods such as salt formation, the use of surfactants, lipid-based drug delivery systems, solid dispersion techniques, and nanocrystal formulations are discussed. Finally, the challenges associated with each strategy, as well as future directions in this field, are considered.
Downloads
Metrics
References
Al-Kassas R, Bansal M et al. Nanosizing techniques for improving bioavailability of drugs. 2017; J Control Release. 260, 202-212
Argade PS, Magar DD et al. Solid Dispersion: Solubility Enhancement Technique for poorly water-soluble Drugs. 2013; J. Adv. Pharm. Edu. & Res. 3(4): 427-439
Bhattacharya SN, Deschenes LA, and Wesley JA. Solubility: It's not just for physical Chemists. 2006, Drug Discov Today; 11 (21/22): 1012-1018.
Bighley LD, Berge SM, and Monkhouse DC, Swarbrick J and Boylan JC. Salt Forms of Drugs and Absorption in Encyclopedia of Pharmaceutical Technology, Eds. Marcel Dekker, New York, 1996; 453-499.
Butler JM and Dressman JB. The Developability Classification System: Application of Biopharmaceutics Concepts to Formulation Development. 2010; J Pharmaceutical Sci. 99(12): 4940-4954
Chow SC. Bioavailability and Bioequivalence in Drug Development. Wiley Interdiscip Rev Comput Stat. 2014;6(4):304-312. doi: 10.1002/wics.1310. PMID: 25215170; PMCID: PMC4157693
Delaney JS. Predicting aqueous solubility from structure. Drug Discov. Today. 2005;10 (4), 289-295
Drescher S, van Hoogevest P. The Phospholipid Research Center: Current Research in Phospholipids and Their Use in Drug Delivery. 2020, Pharmaceutics.12(12):1235. doi: 10.3390/pharmaceutics12121235
Erxleben A. Cocrystal Applications in Drug Delivery. 2020; Pharmaceutics. 12(9):834. doi: 10.3390/pharmaceutics12090834.
Food and Drug Administration Regulatory Classification of Pharmaceutical Co-Crystals, Guidance for Industry. [(accessed on 20 August 2018)];2018 Feb; Available online: https://www.fda.gov/media/81824/download
Florence AT and Attwood D. Properties of the Solid State in Physicochemical Principles of Pharmacy, Eds. Macmillan Press Ltd, London, 3rd ed, 1998; 5–34.
Franco V, Gershkovich P, Perucca E et al. The Interplay Between Liver First-Pass Effect and Lymphatic Absorption of Cannabidiol and Its Implications for Cannabidiol Oral Formulations. Clin Pharmacokinet. 2020; 59, 1493–1500 . https://doi.org/10.1007/s40262-020-00931-w
Hecq J, Deleers M, Fanara D, Vranckx H, Boulanger P, Le Lamer S, Amighi K. Preparation and in vitro/in vivo evaluation of nano-sized crystals for dissolution rate enhancement of ucb-35440-3, a highly-dosed poorly water-soluble weak base. 2006. Eur. J. Pharm. Biopharm. 64 (3), 360-368
Kesisoglou F, Panmai S et al. Nanosizing — Oral formulation development and biopharmaceutical evaluation. 2007. Adv Drug Delivery Reviews. 59(7), 631-644
Leite ER, Giraldi TR, Pontes FM, Longo EA, Beltrán AJ, Andrés J. Crystal growth in colloidal tin oxide nanocrystals induced by coalescence at room temperature. 2003.Appl. Phys. Lett., 83 (8), 1566-1568.
Loh ZH, Samanta AK et al.. Overview of milling techniques for improving the solubility of poorly water-soluble drugs. 2015; Asian J Pharmaceutical Sci. 10(4): 255-274
Rasenack N & Muller BW. Micron‐Size Drug Particles: Common and Novel Micronization Techniques. 2004. Pharmaceutical Dev and Technology. 9(1): 1-13
Salawi A. Self-emulsifying drug delivery systems: a novel approach to deliver drugs. 2022. Drug Deliv. 29(1) 1811-1823.
Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN Pharm. 2012:195727. doi: 10.5402/2012/195727. Epub 2012 Jul 5. PMID: 22830056; PMCID: PMC3399483.
Shahrin N. Solubility and dissolution of drug product: a review. 2013; Int. J Pharm and Life Sciences. 2: 33-41.
Williams H.D., Trevaskis N.L., Charman S.A., Shanker R.M., Charman W.N., Pouton C.W., Porter C.J.H. Strategies to address low drug solubility in discovery and development. 2013, Pharmacol. Rev.; 65:315–499. doi: 10.1124/pr.112.005660
Wu B, Kulkarni K et al. First-Pass Metabolism via UDP-Glucuronosyltransferase: a Barrier to Oral Bioavailability of Phenolics. J Pharma Sci. 2021,100(9): 3655 -3681
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
