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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    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
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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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    ABSTRACT: Resumen Las nanopartículas lipídicas sólidas (SLN) y los transportadores lipídicos nanoestructurados (NLC) son elaboradas mediante diferentes métodos que incluyen la dispersión de una fase oleosa conteniendo diferentes tipos de lípidos sólidos y/o líquidos, en una fase acuosa conteniendo una alta proporción de tensoactivos y co-tensoactivos. Para llegar a obtener dispersiones de partículas nanométricas estables, se requieren métodos de homogenización de alta energía y la formación de un recu- brimiento protector de emulsificantes alrededor de las partículas lipídicas. Este trabajo presenta una perspectiva de los dife - rentes métodos de elaboración de SLN y de NLC, incluyendo los procesos de esterilización y de liofilización. Se discuten las condiciones de operación y su efecto en las características de las partículas, así como la bondad de los procesos para su esca- lamiento y producción en gran escala. Abstract Solid lipid nanoparticles (SLN) and nanostructurated lipid carriers (NLC) are produced by the dispersion of an oil phase contai- ning solid and liquid lipids into an aqueous phase with high surfactants and co-surfactants concentrations. A high energy ho- mogenization procedure and the formation of a surfactant shell protection over the lipid particle surface are required in order to make stable nanoparticles. This paper presents an overview of different SLN and NLC production methods. The operation conditions and the effect of the process variables are discussed, including sterilization and lyophilization processes. The sui - tability of these processes for large scale production is also discussed. Palabras clave: SLN, NLC, nanopartículas lipídicas, métodos de preparación, liofilización, esterilización, homogeneización a alta presión, método de emulsificación-evaporación, méto - do de emulsificación-difusión, microemulsificación.
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