Rationalising polymer selection for supersaturated film forming systems produced by an aerosol spray for the transdermal delivery of methylphenidate.
Film forming systems offer a number of advantages for topical and transdermal drug delivery, in particular enabling production of a supersaturated state which can greatly improve drug absorption and bioavailability. However the suitability of individual film forming polymers to stabilise the supersaturated state and optimise delivery of drugs is not well understood. This study reports the use of differential scanning calorimetry (DSC) to measure the solubility of methylphenidate both as the free base and as the hydrochloride salt in two polymethacrylate copolymers, Eudragit RS (EuRS) and Eudragit E (EuE) and relates this to the ability of films formed using these polymers to deliver methylphenidate across a model membrane. EuRS provided greater methylphenidate delivery when the drug was formulated as the free base in comparison EuE because the lower solubility of the drug in EuRS provided a higher degree of drug saturation in the polymeric film. In contrast EuE provided greater delivery of methylphenidate hydrochloride as EuRS could not prevent its crystallisation from a supersaturated state. Methylphenidate flux across the membrane could be directly related to degree of saturation of the drug in the film formulation as estimated by the drug solubility in the individual polymers demonstrating the importance of drug solubility in the polymer included in film forming systems for topical/transdermal drug delivery. In addition DSC has been demonstrated to be a useful tool for determining the solubility of drugs in polymers used in film forming systems and the approaches outlined here are likely to be useful for predicting the suitability of polymers for particular drugs in film forming transdermal drug delivery systems.
Department of Pharmacy, Pharmacology and Postgraduate Medicine, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UK.
A
A
Edwards
School of Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK.
S
S
Qi
Department of Pharmacy, Pharmacology and Postgraduate Medicine, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UK.
F
F
Liu
Department of Pharmacy, Pharmacology and Postgraduate Medicine, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UK; MedPharm Ltd, Unit 3 Chancellor Court, 50 Occam Road, Surrey Research Park, Guildford GU2 7AB, UK.
M B
MB
Brown
Department of Pharmacy, Pharmacology and Postgraduate Medicine, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UK. Electronic address: w.j.mcauley@herts.ac.uk.
W J
WJ
McAuley
D000279:Administration, Cutaneous; D000336:Aerosols; D002152:Calorimetry, Differential Scanning; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients; D008567:Membranes, Artificial; D008774:Methylphenidate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers; D011109:Polymethacrylic Acids; D012869:Skin Absorption; D012995:Solubility
D000336:Aerosols; D000697:Central Nervous System Stimulants; D005079:Excipients; D008567:Membranes, Artificial; D011108:Polymers; D011109:Polymethacrylic Acids; D008774:Methylphenidate; C038300:methylmethacrylate-methacrylic acid copolymer