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


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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    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. DOI:10.1016/j.ijpharm.2014.10.004; · 3.65 Impact Factor
    • "In each case the lipids were weighed using analytical balance (Adventurer, Ohaus, China), melted together and stirred at a temperature of 70° using a magnetic stirrer (SR1 UM 52188, Remi Equip., India), until a homogenous, transparent white melt was obtained. The homogenous mixture was stirred at room temperature until solidification to obtain the SRMS[113]. "
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    ABSTRACT: The objective of our work was to study the micromeritic properties of lyophilized diclofenac potassium-loaded lipospheres and to evaluate in vivo, the analgesic properties of diclofenac potassium in the lipospheres in addition to other in vitro properties. Solidified reverse micellar solutions were prepared by fusion using 1:1, 2:1, and 1:2% w/w of Phospholipon(®) 90H and Softisan(®) 154. Diclofenac potassium (1, 3, and 5% w/w) was incorporated into the solidified reverse micellar solutions. Solidified reverse micellar solutions-based lipospheres were formulated by melt homogenization techniques using Ultra-Turrax homogenizer, and thereafter lyophilized to obtain water-free lipospheres. The lipospheres were characterized in terms of particle size and morphology, stability, thermal analysis, drug content, encapsulation efficiency, and loading capacity. The flow properties of the lipospheres were studied using both direct and indirect methods of assessing flow. The analgesic properties of the lipospheres were studied using the hot plate method. Results obtained showed that the yield of diclofenac potassium-loaded lipospheres was high and the particle size ranged from 0.61±0.07 to 2.55±0.04 μm. The lipospheres had high encapsulation efficiency of 95%, which was affected by the amount of drug loaded, while the loading capacity increased with the increase in drug loading. Diclofenac potassium-loaded lipospheres exhibited poor flow. The formulations exhibited good analgesic effect compared with the reference and had 84 to 86% drug release at 13 h. The lipospheres based on solidified reverse micellar solutions could be used for oral delivery of diclofenac potassium.
    Indian Journal of Pharmaceutical Sciences 02/2013; 75(3):302-309. DOI:10.4103/0250-474X.117436 · 0.48 Impact Factor
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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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