• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.303-311
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• 1997

Proliposomal patch of clenbuterol, ${\beta}_2-agonist$ bronchodilator, was prepared and its feasibility as a novel transdermal drug delivery system was examined. Proliposomal granules containing clenbuterol was prepared by a standard method using sorbitol and lecithin with (Rx 2) or without cholesterol (Rx 1). The porous structure of sorbitol in the proliposomes was maintained allowing tree flowability of the granules. Following contact with water, the granules were converted probably to liposomes almost completely within several minutes. It indicates that proliposomes may be hydrated, when they are applied on the skin under occlusive condition in vivo, by the sweat to form liposomes. Clenbuterol release from Rx 1 and Rx 2 proliposomes to pH 7.4 isotonic phospate buffer (PBS) across cellulose membrane (mol. wt. cut-off of 12000-14000) was retarded significantly compared with that from the mixture of clenbuterol powder and blank proliposomes. Interestingly, proliposomes prepared with lecithin and cholesterol (i.e., Rx 2 proliposomes) showed much more retarded release of clenbuterol than proliposomes prepared only with lecithin (i.e.. Rx 1 proliposomes), indicating that clenbuterol release from proliposomes can be controlled by the addition of cholesterol to the proliposomes. Proliposomal patches were prepared using PVC film as an occlusive backing sheet, two sides adhesive tape (urethane, 1.45 mm thickness) as a reservoir for proliposome granules and Millipore MF-membrane (0.45 mm pore size) as a drug release-controlling membrane. Rx 1 or Rx 2 proliposomes containing 4.6 mg of clenbuterol were loaded into the reservoir of the patch. Clenbuterol release from the patches to pH 7.4 PBS was determined using USP paddle (50 rpm)-over-disc release method. Clenbuterol release from the proliposomal patches was much more retarded even than from a matrix type clenbuterol patch (Boehringer Ingelheim ltd). Being consistent with clenbuterol release from the proliposomal granules, the release from the patches was highly dependent on the presence of cholesterol in the proliposomes : Patches containing Rx 2 proliposomes showed several fold slower drug release than patches containing Rx 1 proliposomes. When the patch containing Rx 1 proliposomes was applied on to the back of a hair-removed rat, clenbuterol concentration in the rat blood was maintained during 6-72 hrs. Transdermal absorption of clenbuterol from the patch was accelerated when the patch was prehydrated with 50 ml of pH 7.4 PBS before topical application. Above results indicate that sustained transdermal delivery of clenbuterol is feasible using proliposomal patches if the cholesterol content and pore size of the release rate-controlling membrane of patches, for example, are appropriately controlled.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.4
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• pp.301-307
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• 2004

The flap considered at first for the reconstruction of large maxillary defect, especially mid-face defect, is scapular free flap, because it provides ample composite tissue which can be designed 3-dimensionally for orbital, facial and oral reconstruction. In case of maxillary defect involving hard palate, however, this flap has some limitations. First, its bulk prevents oral function and physio-anatomic reconstruction of nasal and oral cavity. Second, mobility and thickness of cutaneous paddle covering the alveolar area reduce retention of tissue-supported denture and give rise to peri-implantitis when implant is installed. Third, lateral border of scapula that is to reconstruct maxillary arch and hold implants is straight, not U-shaped maxillary arch form. To overcome these problems, new concept of step prefabrication technique was provided to a 27-year-old male patient who had been suffering from a complete hard palate and maxillary alveolar ridge defect. In the first stage, scapular osteomuscular flap was elevated, tailored to fit the maxillary defect, particulated autologous bone was placed subperiosteally to simulate U-shaped alveolar process, and then wrapped up with split thickness skin graft(STSG, 0.3mm thickness). Two months later, thus prefabricated new flap was elevated and microtransferred to the palato-maxillary defect. After 6 months, 10 implant fixtures were installed along the reconstructed maxillary alveolus, with following final prosthetic rehabilitation. The procedure was very successful and patient is enjoying normal rigid diet and speech.