Solubilization of poorly-soluble drugs

A key benefit of microemulsions is their ability to disperse food ingredients, such as bioactives, flavors and preservatives, that are poorly water solnble in aqneons systems, as these compounds can be conveniently solubilized into the oil droplets of o/w microannlsions (Weiss et al, 2006). For example, Garti and co-workers (2004) studied the solubilization of water-insoluble and poorly oil-soluble nutrients - phytosterol, lutein and lycopene - in U-type microemulsions and showed an increase in the solubility of these nutrients by factors of 15, 11 and 5, respectively, by incorporating polysorbate 80 (or polysorbate 60) in a limonene-ethanol mixture. 

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Liposomes are widely used in dermal preparations (dermatics) for various reasons. Cyclodextrins play a role in the solubilization of poorly soluble drugs. Hence, their use in dermatics is rarely restricted. 

Although hypromellose and HPMCAS are the dominant cellulosics utilized in the solubilization of poorly soluble drug compounds, most cellulosics accepted as an excipient for pharmaceutical formulation have been studied. These polymers, shown in Table 27.4, include MC, hypromellose phthalate (HPMC-P), EC, carboxymethyl ethylcellulose, hydroxypropyl cellulose, and sodium carboxymethylcellulose. 

In the past few years, ILs gained importance for use in several pharmaceutical applications. They are found to be particularly useful for the solubilization of poorly soluble drugs [35-37]. ILs can also be used to synthesize active pharmaceutical ingredients (APIs) with modified solubility, increased thermal stability, and a significant enhancement in the efficacy of topical analgesia compared to then-starting materials [38-40]. Furthermore, many ILs exhibit antimicrobial activity [41], which can make them useful as APIs or formulation preservatives and also provide unique opportunities for oral [42] and topical drug delivery [43]. 

Kawakami, K., K. Miyoshi, andY. Ida (2004). Solubilization behavior of poorly soluble drugs with combined use of gelucire 44/14 and cosolvedtPharm. Sci., 93 1471-1479. 

During the last two decades, significant efforts have been made in the development of solubilization systems for poorly soluble drugs. As listed in Table 1, various methods have been explored to increase water solubilities of poorly soluble drugs. 

A preferred location of the solubilizate molecule within the micelle is largely dictated by chemical structure. However, solubilized systems are dynamic and the location of molecules within the micelle changes rapidly with time. Solubilization in surfactant aqueous systems above the critical micelle concentration offers one pathway for the formulation of poorly soluble drugs. From a quantitative point of view, the solubilization process above the CMC may be considered to involve a simple partition phenomenon between an aqueous and a micellar phase. Thus the relationship between surfactant concentration Cm and drug solubility Ctot is given by Eq. (3). 

Sezgin Zerrin, Yuksel Nilufer, and Baykara Tamer. Preparation and characterization of polymeric micelles for solubilization of poorly soluble anticancer drugs. Eur. J. Pharm. Biopharm. 64 no. 3 (2006) 261-268. 

The above discussion clearly demonstrates that solubilization above the cmc offers an approach to formulation of poorly soluble drugs. This approach has several limitations finite capacity of micelles for the drug short- or long-term adverse effects solubilization of other ingredients such as preservatives, flavors and coloring agents, which may cause alterations in stability and effectiveness. 

Solubilization in surfactant solutions above the critical micelle concentration offers one approach to the formulation of poorly soluble drugs in solution form [ ] ... 

Though povidone is used in a variety of pharmaceutical formulations, it is primarily used in solid-dosage forms. In tableting, povidone solutions are used as binders in wet-granulation processes. Povidone is also added to powder blends in the dry form and granulated in situ by the addition of water, alcohol, or hydroalcoholic solutions. Povidone is used as a solubilizer in oral and parenteral formulations, and has been shown to enhance dissolution of poorly soluble drugs from solid-dosage forms. 

Uses Wet granulation binder for oral solid dosage forms solubilizer and bioavailability enhancer of poorly soluble drugs crystal growth inhibitor, and rheological additives in soft-gelatin capsules, oral liquids and suspensions, parenterals, topical gels, creams, lotions and ophthalmic preps. 

For highly permeable, poorly soluble drugs given in lower doses, the dissolution rate rather than the saturation solubility is the limiting factor. An increase in dissolution rate due to in vivo solubilization mediated by food intake could theoretically be obtained, but this situation is not always found in vivo. For example, food does not affect the rate and extent of bioavailability for candesartan cilexitil, a very poorly soluble compound [78], An in vitro dissolution and solubility study of this compound in simulated intestinal media provided a potential explanation it was revealed that the solubility was increased as a function of bile concentration as expected, whereas the dissolution rate was not increased by the higher bile concentrations being representative for the fed state (see Fig. 21.14). Thus, although... 

The pharmaceutical literature abounds with examples of how poorly soluble drug substances have been solubilized through the formation of molecular complexes. 

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