Enhancement of the Solubility of Poorly Water Soluble Drugs through Solid Dispersion: A Comprehensive Review

Abstract

Absorption of a drug through the oral route involves its dissolution from the formulation into gastric and/ or intestinal fluids followed by its permeation through gastrointestinal cell membranes and finally into the systemic circulation. Oral solid dosage forms are one of the most commonly used formulation types having multiple benefits over other formulations/routes. However, the challenge for a pharmaceutical scientist lies in the fact that dissolution of a drug from an oral solid formulation (a key factor in drug absorption) is dependent on the aqueous solubility of the drug. Therefore, a drug with poor aqueous solubility would exhibit dissolution rate limited absorption and similarly a drug possessing poor membrane permeability undergo permeation rate limited absorption. A drug is highly soluble when highest dose of drug is soluble in ≤250 ml of water over a pH range of 1 to 7.5 and a drug is highly permeable when extent of absorption in humans is to be ≥90% of an administered dose [1] . It has been investigated that most of new chemical entities currently being discovered and intended to be used as a solid dosage form should produce an efficient and reproducible plasma concentration after oral administration. However, most of them tend to have poor water solubility, which limits the therapeutic efficacy of that drug. Moreover, poor solubility results in increased dose and frequent administration leading to higher incidences of side-effects [2][3][4][5][6] . Hence, pharmaceutical research has emphasised on elevating the oral bioavailability of poorly water-soluble drugs by improving their solubility, dissolution rate and membrane permeability. Solubility is an important determinant in drug liberation and hence drug absorption, which plays a key role in oral bioavailability of formulations. The dissolution rate of a drug directly depends upon its solubility. Most of the new drugs have poor water solubility; thereby pose a difficulty in formulating into drug delivery systems. Therefore, solubility enhancement of poorly water soluble drugs is one of the necessary preformulation steps in the pharmaceutical product development research. Solid dispersion is a unique and promising approach for enhancing the dissolution characteristics and oral bioavailability of poorly water-soluble drugs. The present review highlights portrayal of solid dispersions, its types including eutectic mixtures and solid solutions, method of preparation and also the useful carriers for the preparation of solid dispersions. Furthermore, the wide research conducted hitherto on solid dispersions for enhancing solubility of different efficacious drugs, challenges encountered in the development of solid dispersions and recent advancements to overcome its pitfalls have also been elaborated.

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“…Dispersions: Solvent Evaporation Method: 11 Formulations of fluconazole solid dispersions were prepared using different carriers like PEG 4000 and PEG 6000 10,9,5 in various proportions, i.e., 1:1, 1:2, 1:3 (Drug: Carrier) as shown in Table 1. The drug and the carriers or polymers were dissolved in ethanol in a beaker.…”

“…The solid dispersion obtained was sieved through # 60 sieve and stored inside the desiccator for further use. Kneading Method: 12 Formulations of Fluconazole solid dispersions were prepared using different carriers like β-cyclodextrin 7,8 , Gelucire 44/14 13 , Gelucire 50/13 14 , PVP K30 9,11 , PEG 4000 and PEG 60005 5,8,10 in various proportions i.e., 1:1, 1:2, 1:3, 1:4, 1:5 (Drug: Carrier) as shown in Table 2. Polymers were added to the mortar and pastel, and to this small quantity of ethanol were added during trituration to obtain good slurry-like consistency.…”

“…For a drug to undergo complete absorption and have good bioavailability it must be dissolved in gastric fluids. Dissolution is a process that determines the degree and the rate of absorption of the drugs 5 . Drugs having slow dissolution rates often show erratic and incomplete absorption, which causes bioavailability problems when they are administered orally.…”

“…Solid dispersion is a method in which hydrophobic drugs are dispersed in a fine state in hydrophilic carriers 6 . The various carriers or polymers used for preparation of solid dispersions are β-cyclodextrin 7,8 , pyrolidone (PVP) 9 , urea, mannitol, polyethylene glycols (PEG) 5,10 etc.…”

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“…The therapeutic effectiveness of a drug depends upon the bioavailability and ultimately is attributed to the solubility of drug moiety 2 . Presently, numerous formulation technologies are available to enhance solubility as well as dissolution profile to enhance oral bioavailability 3 .…”