Influence of poloxamers on the dissolution performance and stability of controlled-release formulations containing Precirol ATO 5.
Lipid excipients are usually used for the development of sustained-release formulations. When used in relatively high quantities, Precirol ATO 5 imparts sustained-release properties to solid oral dosage forms, by forming a lipid matrix. To control or adjust the drug release kinetics from such lipid matrix however, one must often resort to complementary ingredients or techniques. This study investigates the influence of poloxamers (Lutrol) included in lipid matrices composed of glyceryl palmitostearate (Precirol ATO 5) on their dissolution performance and their stability. The addition of these hydrophilic polymers in the lipid matrix increased the amount of theophylline released thanks to the swelling of the hydrophilic polymer and the creation of a porous network into the inert lipid matrix. The grade and the quantity of Lutrol could modulate the extent of drug release. Theophylline was released mainly by the matrix erosion but also by diffusion through the pores as suggested by the Peppas' model. Moreover, the addition of Lutrol enhanced the stability during storage. The theophylline release was quite steady after 6 months in different conditions (temperature and humidity). Thus, the mixture of glyceryl palmitostearate and poloxamers is an approach with many advantages for the development of controlled-release formulations by capsule molding.
Jannin
V
V
Pharmaceutical Development Laboratory, Gattefossé S.A.S., BP 603, F-69804 Saint-Priest Cedex, France. vjannin@gattefosse.com
Pochard
E
E
Chambin
O
O
D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations; D004075:Diglycerides / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D066298:In Vitro Techniques; D007700:Kinetics; D008854:Microscopy, Electron / Q000379:methods; D008956:Models, Chemical; D020442:Poloxamer / Q000737:chemistry*; D016062:Porosity; D012212:Rheology; D012995:Solubility; D013678:Technology, Pharmaceutical; D013806:Theophylline / Q000737:chemistry*; D014783:Viscosity; D014867:Water / Q000737:chemistry
D003692:Delayed-Action Preparations; D004075:Diglycerides; D005079:Excipients; D014867:Water; D020442:Poloxamer; D013806:Theophylline; C009032:precirol