Article

Drug release and permeation studies of nanosuspensions based on solidified reverse micellar solutions (SRMS)

Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Mendelssohnstrasse 1, D-38106 Braunschweig, Germany.
International Journal of Pharmaceutics (Impact Factor: 3.65). 12/2005; 305(1-2):167-75. DOI: 10.1016/j.ijpharm.2005.09.007
Source: PubMed

ABSTRACT Solidified reverse micellar solutions (SRMS), i.e. mixtures of lecithin and triglycerides, offer high solubilisation capacities for different types of drugs in contrast to simple triglyceride systems [Friedrich, I., Müller-Goymann, C.C., 2003. Characterisation of SRMS and production development of SRMS-based nanosuspensions. Eur. J. Pharm. Biopharm. 56, 111-119]. Nanosuspensions based on SRMS were prepared by homogenisation close to the melting point of the SRMS matrix. In a first step the SRMS matrices of 1:1 (w/w) ratios of lecithin and triglycerides were loaded with 17beta-estradiol-hemihydrate (EST), hydrocortisone (HC) or pilocarpine base (PB), respectively, and subsequently ground in liquid nitrogen to minimise drug diffusion later on. The powder was then dispersed in a polysorbate 80 solution using high pressure homogenisation. The drug loading capacities of the nanosuspensions were very high in the case of poorly water-soluble EST (99% of total 0.1%, w/w, EST) and HC (97% of total 0.5%, w/w, HC) but not sufficient with the more hydrophilic PB (37-40% of total 1.0%, w/w, PB). These findings suggest SRMS-based nanosuspensions to be promising aqueous drug carrier systems for poorly soluble drugs like EST and HC. Furthermore, in vitro drug permeation from the different drug-loaded nanosuspensions was performed across human cornea construct (HCC) as an organotypical cell culture model. PB permeation did not differ from the nanosuspension and an aqueous solution whereas the permeation coefficients of HC-loaded nanosuspensions were reduced in comparison to aqueous and oily solutions of HC. However, the permeated amount was higher from the nanosuspensions due to a much lower HC concentration in the solution than that in the nanosuspension (solution 0.02%, w/w, versus nanosuspension 0.5%, w/w). The high drug load of the nanoparticles provides prolonged HC release. Permeated amounts of EST were reduced in comparison to HC and only detectable with an ELISA technique. The EST release from nanosuspensions and different EST-loaded systems revealed a prolonged EST release from the nanoparticulate systems in contrast to a faster release of an oily solution of an equal EST concentration. With regard to an aqueous EST suspension of similar concentration which represents a depot system the release rate from the nanosuspensions revealed the same order of magnitude which points again to a prolonged release potential of the nanosuspensions.

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    • "Before initiating formulation development studies of ARTloaded NLC, it was considered essential to investigate the thermal stability of ART to determine the feasibility of using hot homogenization to produce the NLC formulations. Thermal gravimetric analysis (TGA) has been previously used and recommended as a simple and rapid method to determine the thermal stability of APIs (Souto et al., 2005; Teeranachaideekul et al., 2008; Friedrich et al., 2005). Consequently, the thermal stability of ART was investigated using a TGA 4000 (Pyris 6 TGA, PerkinElmer, Inc., Waltham, MA 02451, USA). "
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    • "The permeation coefficient P was calculated as the quotient of the flux J, and the initial drug concentration C, in the patches placed on the skin mounted in the donor compartment of the Franz cell (Mundargi et al., 2007; Ganesh et al., 2011; Attama et al., 2009). The permeation data (permeation coefficient and steady-state flux values) obtained from the study were within the range obtained for some lipophilic and lipophobic drugs (Valenta and Auner, 2004; Ganesh et al., 2011; Bazigha et al., 2011; Attama et al., 2008; Friedrich et al., 2005). Since PURASORB ® PL 32-based patches gave the highest permeation flux and coefficients, it implies that sustained release gentamicin dosage form might be developed with this formulation. "
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