Solubility drug formulation

Pouton, C. Formulation of poorly water-soluble drugs for oral administration Physicochemical and physiological issues and the lipid formulation classification system. Eur. J. Pharm. Sci. 2006, 29, 278-287. 

Fig. 6 Solubility effects on drug stability curve A, drug formulated as lOmg/mL solution (q/2 = 1 year) curve B, drug formulated as a suspension with a saturated solubility of 1 mg/mL (ti/2 = 7.3 years). 

Nanosuspensions for the Formulation of Poorly Soluble Drugs. Stuttgart Medpharm Scientific Publishers, 1998, pp 149-174. 

SH Klang, M Parnas, S Benita. Emulsions as drug carriers - possibilities, limitations and future perspectives. In RH Muller, S. Benita, BHL Bohm, eds. Emulsions and Nanosuspensions for the Formulation of Poorly Soluble Drugs. Stuttgart Medpharm Scientific Publishers, 1998, pp 31-78. 

RH Muller, K Peters. Nanosuspensions for the formulation of poorly soluble drugs I.Preparation by a size-reduction technique. Int J Pharm 160(2) 229-237, 1998. 

In the current era with widespread problems of poor solubility [4] a compound (drug) with average permeability and a projected clinical potency of 1 mg kg-1 needs a minimum aqueous solubility of 50-100 jug mL-1 to avoid the use of nonstandard solubility fixing formulation technology. The guidelines published by Pfizer s Curatolo on maximum absorbable dose are an excellent guide for the combination of permeability, solubility and potency required in an orally active drug [8],... 

Araya H, Tomita M, Hayashi M (2006) The novel formulation design of self-emulsifying drug delivery systems (SEDDS) type O/W microemulsion III The permeation mechanism of a poorly water soluble drug entrapped O/W microemulsion in rat isolated intestinal membrane by the Ussing chamber method. Drug Metab Pharmacokinet 21 45-53. 

The sample must be soluble If it s not in solution, it cannot be analyzed by HPLC. Although this may seem obvious, solubility issues complicate real assays of low-solubility drugs and controlled-release formulations. Many situations encountered in pharmaceutical analysis, such as low recovery, lack of mass balance, and out-of-specification results, might stem from solubility problems in a sample preparation step, rather than the HPLC analysis itself. 

Recently, Yoshikawa et al. [70] reported a new in vitro dissolution test, called the rotating beads method, for drugs formulated in pressure-controlled colon delivery capsules. This dissolution method was applied to acetominophen sustained-release tablets and two other drugs having low solubility in the colon, tegafur and 5-ASA. There was good correlation between the in vitro dissolution rates and the in vivo absorption rates. 

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