Drug release and permeation studies of nanosuspensions based on solidified reverse micellar solutions (SRMS).
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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ABSTRACT: A novel adapalene-loaded solid lipid microparticle (SLMA) dispersion as a topical drug delivery system (TDDS) for follicular penetration has been introduced. The objective of the present study was to investigate the rheological properties, the follicular penetration with differential tape stripping on porcine ear skin, the drug release in sebum and stratum corneum (SC) lipid mixtures, and the permeation behavior across human SC in comparison to a commercially available cream as standard. Physicochemical characterization reveals that adapalene is homogeneously distributed within the SLMA dispersion and chemically stable for at least 24 weeks. The SLMA dispersion shows a lower complex viscosity at 20°C and a higher one at 32°C than the cream, while the phase angle of the dispersion is always larger at both temperatures. Both formulations feature an equivalent potential for follicular penetration and deposition. However, the superiority of the SLMA dispersion is based on the preferential drug release in sebum while there is no or just a slight release in SC lipids and no permeation for both formulations. Due to the similarity of the glyceride matrix of the SLMA to sebum components, a targeted drug delivery into sebum and thereby an increased follicular penetration may be facilitated. Copyright © 2014. Published by Elsevier B.V.European Journal of Pharmaceutics and Biopharmaceutics 10/2014; · 4.25 Impact Factor
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ABSTRACT: NLC topical formulation as an alternative to oral and parenteral (IM) delivery of artemether (ART), a poorly water-soluble drug was designed. A Phospholipon 85G-modified Gelucire 43/01 based NLC formulation containing 75% Transcutol was chosen from DSC studies and loaded with gradient concentration of ART (100–750 mg). ART-loaded NLCs were stable (À22 to À40 mV), polydispersed (0.4–0.7) with d90 size distribution range of 247–530 nm without microparticles up to one month of storage. The encapsulation efficiency (EE%) for ART in the NLC was concentration independent as 250 mg of ART loading achieved $61%. DSC confirmed molecular dispersion of ART due to low matrix crystallinity (0.028 J/g). Ex vivo study showed detectable ART amounts after 20 h which gradually increased over 48 h achieving $26% cumulative amount permeated irrespective of the applied dose. This proves that ART permeates excised human epidermis, where the current formulation served as a reservoir to gradually control drug release over an extended period of time. Full thickness skin study therefore may confirm if this is a positive signal to hope for a topical delivery system of ART. ã 2014 Elsevier B.V. All rights reserved.International Journal of Pharmaceutics 10/2014; 477:208-217. · 3.79 Impact Factor
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ABSTRACT: The objectives of this research were to formulate and evaluate solidified reverse micellar solution (SRMS)-based tablets for oral administration of gentamicin. SRMS matrices formulated with Phospholipon® 90G and Softisan® 154 at ratios 1:1, 1:2 and 2:1 were used to prepare gentamicin tablets by meltsolidification. Characterization based on surface morphology, weight uniformity, softening/liquefaction time, friability, hardness/crushing strength, erosion time and absolute drug content were carried out on the tablets. The in vitro release studies were performed in distilled water, simulated gastric fluid without pepsin (SGF, pH 1.2) and simulated intestinal fluid without pancreatin (SIF, pH 7.4 ) , while the in vivo release studies were conducted using rats. The results obtained showed that thee tablets were smooth and circular in shape, maintained a percentage deviation of 3 - 5% in the weight uniformity test, had percentage average resistances (friability) less than 1% and crushing strengths less than 5 kgf, and thus conformed to compendial requirements for acceptance. In vitro release studies indicated that incorporation of greater amounts of Softisan® 154 than Phospholipon® 90G caused a significant (p<0.05) increase in drug release. Further kinetic analysis of drug release showed predominance of the Higuchi square root model with r2 = 0.999. In vivo release studies revealed significant (p<0.05) release of gentamicin from all the tablet batches. The result of this study gave insight that the issue of gentamicin stability in oral formulations could be adequately addressed by tactical engineering of lipid drug delivery systems such as SRMS-based tablets.Journal of Pharmacy Research. 01/2012; 20125:4914-4920.