Oral and Injectable Formulations

Sirolimus is insoluble in water, having poor systemic bioavailability estimated at 18% following ingestion of the tablet. The polymers, polyethylene glycol 8000, polyethylene glycol 20000, and poloxamer 188 (a nonionic amphiphilic copolymer surfactant) augment water solubility and miscibility of SRL tablets [1]. Though SRL tablets are taken just once daily, this does not constitute an extended- or delayed-release formulation per se, as the half-life of SRL is approximately 60 hours. 

Given our ability to enhance the physicochemical behavior of this immunosuppressive drug using polymer-based formulation systems, we anticipate an alleviation of select adverse effects using disparate pharmaceutical dosage formulation strategies. 

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Strickley RG. Solubilizing excipients in oral and injectable formulations. Pharm Res 2004 21 201. 

Certain kinds of improvements are possible in almost every dosage form. Besides oral and injectable formulations, CD inclusion has been shown to improve bioavailability of compounds administered by other routes, including ocular, topical, nasal, and rectal routes (Uekama et al., 1994 Marttin et al., 1998 Bary et al., 2001 Loftsson and Masson, 2001 Rode et al., 2003). Some important applications particularly applicable for insoluble compounds are summarized below. 

Strickley (2004) has compiled a comprehensive review of solubilizing excipients, including surfactants, in various oral and injectable formulations. 

Oral and injectable formulations of different steroids are often "stacked," ie, used simultaneously. Because detection of these different steroids is difficult and expensive, the history from the patient rather than urine toxicology is more generally useful for detecting anabolic steroid abuse. Anabolic steroids were added to Schedule III of the Controlled Substances Act in 1990. 

Strickley RG. Solubilizing Excipients in Oral and Injectable Formulations. Pharm Res OOA 21 201-230. 

Produced by Sireptomyces fcanamyceri-cus available in oral and injectable formulations used for short-term treatment of serious infections. 

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