Advancement in Solubilization Approaches: A Step towards Bioavailability Enhancement of Poorly Soluble Drugs

Abstract

A drug’s aqueous solubility is defined as the ability to dissolve in a particular solvent, and it is currently a major hurdle in bringing new drug molecules to the market. According to some estimates, up to 40% of commercialized products and 70–90% of drug candidates in the development stage are poorly soluble, which results in low bioavailability, diminished therapeutic effects, and dosage escalation. Because of this, solubility must be taken into consideration when developing and fabricating pharmaceutical products. To date, a number of approaches have been investigated to address the problem of poor solubility. This review article attempts to summarize several conventional methods utilized to increase the solubility of poorly soluble drugs. These methods include the principles of physical and chemical approaches such as particle size reduction, solid dispersion, supercritical fluid technology, cryogenic technology, inclusion complex formation techniques, and floating granules. It includes structural modification (i.e., prodrug, salt formation, co-crystallization, use of co-solvents, hydrotrophy, polymorphs, amorphous solid dispersions, and pH variation). Various nanotechnological approaches such as liposomes, nanoparticles, dendrimers, micelles, metal organic frameworks, nanogels, nanoemulsions, nanosuspension, carbon nanotubes, and so forth have also been widely investigated for solubility enhancement. All these approaches have brought forward the enhancement of the bioavailability of orally administered drugs by improving the solubility of poorly water-soluble drugs. However, the solubility issues have not been completely resolved, owing to several challenges associated with current approaches, such as reproducibility in large scale production. Considering that there is no universal approach for solving solubility issues, more research is needed to simplify the existing technologies, which could increase the number of commercially available products employing these techniques.

New insights of propolis nanoformulation and its therapeutic potential in human diseases

“…There are limited therapeutic uses in drug delivery research and development. In fact, it is estimated that 40 % of drugs have been marketed and 90 % of drugs have not undergone pharmacological determination [ 28 ]. Nano formulations have been designed to make propolis more soluble to improve its effectiveness in dosage, pharmacokinetics, solubility, sustained drug delivery, and safety.…”

Solid dispersion systems for enhanced dissolution of poorly water-soluble candesartan cilexetil: In vitro evaluation and simulated pharmacokinetics studies

“…About 70% of current candidate new drugs have poor water solubility; therefore, several solubility improvement strategies have been investigated over the past few decades to enhance drug solubility and bioavailability. Some of these techniques are size reduction by microparticulate system [ 4 ], dendrimers [ 5 ], chemical modification, pro-drug, and salt formation, co-crystals, co-solvency, complexation with cyclodextrin, pH modification, self-emulsifying drug delivery system, and solid dispersion systems (SDSs) [ 6 ]. Each of these methods has its advantages and limitations.…”

The Influence of PVP Polymer Topology on the Liquid Crystalline Order of Itraconazole in Binary Systems

“…One of them is the very poor solubility of a large number of active pharmaceutical ingredients (APIs) and, consequently, their low bioavailability . Hence, in recent years, many scientific groups have been working on various strategies to increase the solubility and therapeutic effectiveness of APIs. − In this context, one can mention several methods, e.g., salt formation, cocrystallization, , micronization, or amorphization . The latter technique, i.e., the transformation of the crystalline active substance into the fully disordered (amorphous) form, is a highly promising research direction .…”