Solubility formulating poorly soluble drugs

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. 

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. 

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. 

Benzoic acids substituted with a basic side chain also are also of interest as pro-moieties whose physicochemical properties and rates of enzymatic hydrolysis can readily be modulated. A number of drugs have been converted to prodrugs with this type of pro-moiety, e.g., hydrocortisone, prednisolone, acyclovir, chloramphenicol, and paracetamol [148] [149], These prodrugs appear well suited as parenteral formulations, being water-soluble, stable in slightly acidic solution, and readily hydrolyzed enzymatically. As examples, we consider here the hydrolysis in human plasma of a number of (aminomethyl)ben-zoates of metronidazole (8.109-8.115, Sect. 8.5.5.1, Table 8.9) [138], These prodrugs are very rapidly activated, which may be beneficial for parenteral administration. However, this type of pro-moiety may be cleaved too rapidly after oral administration to be of interest for poorly absorbed drugs. 

The initial formulation for most drugs is to allow basic in vivo toxicology, pharmacology and biopharmaceutical assessments to be conducted. Aqueous solutions for injection are optimum for this application since the entire dose is administered at a single time point and the problem of bioavailability does not arise. It is important that these formulations are considered carefully, particularly for drugs that are poorly water soluble, because potentially useful compounds may be rejected inadvertently. These early formulations are also crucial because they set an in vivo benchmark for the drug s future performance. 

Non-ionic surfactants are used in formulations to solubilise drugs with poor water solubility these compounds consist in their simplest form of an alkyl group attached to a polyethylene glycol chain. Non-ionic surfactants are usually mixtures, e.g. Cetomacrogol 1000, which has the general formula ... 

Another method of improving bioavailability for these poorly soluble drugs is to prepare an amorphous formulation, since an amorphous form allows fasterdissolution of the drug in comparison to its corresponding crystalline form. An amorphous formulation is prepared by incorporating the... 

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