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Liposomal diltiazem HCl as ocular drug delivery system for glaucoma.

Drug development and industrial pharmacy (2013-04-11)
Mahmoud Mokhtar Ibrahim, Salma A H Tawfique, Mahmoud M Mahdy
ABSTRACT

In this study, unilamellar liposomal vesicles of diltiazem HCl (DH) were prepared using either reversed phase evaporation (REV) or proliposome methods. Soya phosphatidylcholine (SPC) was used for preparing the liposomes, and the vesicles were rigidified using cholesterol (Chol) or cetyl alcohol (CA) in different molarities. The major differences in both the entrapment efficiency percent (EE%) and drug release were evaluated as a function of the method of preparation, Chol or CA contents, and charging lipids. Moreover, the morphology of the vesicles was confirmed by transmission electron microscopy. The effects of Chol or CA incorporation into the liposomes were discussed based on thermal analysis. The in vivo evaluation of liposomal DH was assessed using intra-ocular pressure (IOP), reducing effects in rabbit eyes. Liposomes prepared via REV exhibited higher EE% and lower release rates when compared with those prepared from proliposomes. The incorporation of either Chol or CA in the liposomes enhanced the EE% and decreased the release rates; however, Chol yielded higher results than CA. In addition, both dicetyl phosphate (DCP; negative charge inducer) and stearyl amine (SA, positive charge inducer) decreased the EE% and increased the DH release rate. The in vivo antiglaucoma effects of the liposomes were calculated according to the area above the IOP/Time curve, the maximum response and the time for the maximum response and were compared with effects of the DH solution. The results were in the following order: DH solution < SPC/CA (REV) < SPC/Chol/DCP(REV) < SPC/Chol (proliposomes) < SPC/Chol/SA(REV) < SPC/Chol (REV).

MATERIALS
Product Number
Brand
Product Description

Supelco
Cholesterol solution, certified reference material, 10 mg/mL in chloroform
Sigma-Aldrich
1-Hexadecanol, ≥99%
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1-Hexadecanol, ReagentPlus®, 99%
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1-Hexadecanol, 95%
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Cholesterol, powder, BioReagent, suitable for cell culture, ≥99%
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Cholesterol, Sigma Grade, ≥99%
Sigma-Aldrich
SyntheChol® NS0 Supplement, 500 ×, synthetic cholesterol, animal component-free, aqueous solution, sterile-filtered, suitable for cell culture
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Cholesterol, from sheep wool, ≥92.5% (GC), powder
SAFC
Cholesterol, from sheep wool, Controlled origin, meets USP/NF testing specifications
Supelco
Cholesterol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Cetyl alcohol, SAJ special grade, ≥98.0%
Supelco
Cetyl Alcohol, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Cetyl alcohol, United States Pharmacopeia (USP) Reference Standard
Supelco
Cetyl alcohol, analytical standard
SAFC
Cholesterol, Plant-Derived, SyntheChol®
Cetyl alcohol, European Pharmacopoeia (EP) Reference Standard