Novel Nano-Technologies to Enhance Drug Solubility, Dissolution and Bioavailability of Poorly Water-Soluble Drugs

Abstract

For any drug to be therapeutically efficacious it must enter the systemic circulation and in order to do so, the administered drug must be dissolved in the GIT. Approximately 40 % of drugs developed in the past and about 70-90 % of drugs in development were found to be poorly water soluble. Various pharmaceutical particle technologies are applied to enhance the aqueous solubility of poorly soluble drugs that restrict in vivo bioavailability upon oral administration due to their low dissolution rate in gastrointestinal fluids. The approach involves from traditional to modern particle technologies such as micronization, complexation, nano-suspension, and others. The employed technologies modify the drug’s solubility properties, produce drug forms that are readily soluble in water and can be easily formulated into different dosage forms. The aim of this review paper is to summarize the key aspects of currently used particle technologies to enhance the solubility, dissolution and bioavailability of poorly water-soluble drugs.

Introduction

Drug solubility is the maximum concentration of the drug solute dissolved in the solvent under specific condition of temperature, pH and pressure. The solubility of a drug in saturated solution is a static feature, whereas the rate at which it dissolves is a dynamic property that is more directly related to bioavailability. The pace and degree of medication absorption, as well as its bioavailability, are governed by solubility, dissolution, and gastrointestinal permeability [1].

Oral treatment of medications is still the preferred method of delivery due to its numerous benefits, including ease of administration, high patient concordance, and economic viability. A medication first dissolves into gastrointestinal fluids in order to absorb in the systemic circulation and reach its site of action when delivered orally. The number of poorly soluble drugs has been greatly increased by combinatorial chemistry, computational molecular modelling, and high-throughput screening in drug discovery. Around 40% of the existing pharmaceutical drugs and about 70-90% of the drugs in the research pipeline are found to be poorly water soluble [2].

The absorption of the drugs from the gastrointestinal tract (GI) after oral administration is governed by the aqueous solubility which is an essential property for any drugs [3, 4]. The most significant challenges currently faced by many pharmaceutical industries is to improve solubility and bioavailability of poorly soluble drugs. Novel particle approaches adopted to enhance the solubility, dissolution and bioavailability properties of poorly soluble drugs are different from available conventional pharmaceutical techniques [5].

The Biopharmaceutics classification system is a scientific framework for classifying drugs on the basis of their solubility and permeability. A drug compound is considered to be highly soluble when the highest dose strength is soluble in 250 mL or less of aqueous media within the pH range of 1 – 6.8 at a temperature of 37 ± 1°C. The 250 mL volume estimate is derived from standard bioequivalence study protocols that recommend drug product administration to fasting human volunteers with an 8 fluid ounce glass of water. Permeability limit of any drug is determined by measuring rate of mass transfer of a drug through human intestinal membrane or non-human systems such as animal or in-vitro culture methods. A drug agent is found to be highly permeable when the degree of absorption in humans is measured to be >/= 90% of the given dose in comparison to an intravenous dose [6]. BCS is considered as an important tool in the development of oral drug products. Two major attributes of drugs are taken into consideration by BCS classification, i.e. solubility and intestinal permeability which control the extent of absorption after oral administration of solid oral dosage form and finally its bioavailability [7].

BCS Class I drugs have high solubility and high permeability so they are well absorbed from the gastrointestinal tract and have high bioavailability after oral administration. When dissolved, BCS class II medicines show poor water solubility, but are well absorbed from the GIT. Because the rate of in-vivo dissolution is often the rate limiting step in the absorption of class II drugs, improving the solubility and dissolution properties might prove useful to improve their bioavailability. BCS class III medicines show high solubility and low permeability, making them difficult to pass through bio membranes. Bioavailability is restricted by permeability rate; however, dissolution is likely to happen quickly. Addition of absorption enhancers in immediate release solid dosage formulation for class III drug is viable option to improve their permeability. Drugs in BCS class IV category show low water solubility and membrane permeability, making them poor candidates for formulation development because improving solubility and dissolution alone may not be enough to increase the bioavailability. Unfortunately, most new developed drugs are poor water soluble, hydrophobic molecules or in other terms; Class II or Class IV drug compounds [8].

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Following excipients are mentioned in the study besides other: Fujicalin, Neusilin, Poloxamer 408, Tween 80, and Gelucire 44/14, PEG 400

Komal Parmar , Rajendra Patel, Novel Nano-Technologies to Enhance Drug Solubility, Dissolution and Bioavailability of Poorly Water-Soluble Drugs, Biomaterials Connect, 2025, Vol. 1, Cite as: doi:10.x/journal.x.x.x, Disclaimer : This is not the final version of the article. Changes may occur when the manuscript is published in its final format.

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