381619 Advanced Structuring of Lipids for Controlled Drug Release; polymorphic crystallizations and curing effects

Tuesday, November 18, 2014: 2:10 PM
202 (Hilton Atlanta)
Diogo Gomes Lopes1, Katrin Becker2, Eva Faulhammer1, Detlev Haack3, Dirk Lochmann4, Johannes G. Khinast1,5, Andreas Zimmer2 and Sharareh Salar-Behzadi1, (1)Research Center Pharmaceutical Engineering (RCPE) GmbH, Graz, Austria, (2)Department of Pharmaceutical Technology, University of Graz, Graz, Austria, (3)Hermes Arzneimittel GmbH, Munich, Germany, (4)CREMER OLEO GmbH & Co. KG, Witten, Germany, (5)Graz University of Technology, Graz

A recent strategy for improving patient adherence to medication is the development of "direct to mouth" multi-particulate drug delivery systems, which strike a good and balanced compromise between taste masking and controlled drug release, taking both immediate and extended release into account. Such systems play a key role in the medication of patients from the geriatric or paediatric population suffering from dysphagia. Hot-melt coating in a fluid bed coater is a suitable technology for manufacturing of such products, offering numerous advantages for the pharmaceutical industries. For instance no need of solvents leads to significantly shorter processing times by sparing time and cost consuming solvent evaporation and recovery steps. The materials commonly used are lipid-based and hence offer further advantages such as toxicological harmlessness and natural availability at a low price point. The challenge is however, their polymorphic stability.

This abstract presents the advanced structuring of lipids by controlling their polymorphic behavior utilizing hot melt technology to provide products with controlled release profile.

Extended release profile: Highly water-soluble drug model, citric acid, was hot melt coated with tristearin. Different inlet temperatures were successfully used for re-crystallization of lipid to provide unstable α polymorph (process A) and stable β polymorph (process B) respectively. An additional third structure was created by curing the coating A into β-form in a heating oven with blooming occurring in the inner and outer surfaces of microcapsules (process AB). The low temperatures used in process A permitted to recover nearly 100% of coating in the α form. All three coatings exhibited the drug release mechanisms expected: an initial slight burst; a zero-order phase; and a Higuchi diffusion process based on the Fick’s law, square root time dependent. However the choice of the polymorphic crystallization had a tremendous impact on the release kinetic slowing the drug release but improving the partition form core to coating.

Immediate release profile: A polymorphic stable formulation containing tripalmitin and additives was successfully developed, which showed an immediate release profile (85% of release within 30 minutes), an adequate taste masking (pH 3.5 in more than 60 s) and no changes in the polymorphism and the dissolution profile during storage for six months at different. A further advantage is the low process temperature of 25°C, which is necessary for the processing of thermolabile substances.

We showed the successful controlling of polymorphic behaviour of lipids, to use them as advanced safe excipients for development of multi-particulate systems with various release profiles.

Extended Abstract: File Not Uploaded