A method to prepare solid lipid nanoparticles with improved entrapment efficiency of hydrophilic drugs

Current Nanoscience (Impact Factor: 1.36). 01/2013; 9(2):211-220. DOI: 10.2174/1573413711309020008

ABSTRACT Introduction: Premise of the present study was to suitably select or modify the constitution of the lipid matrix to achieve significantly high entrapment of hydrophilic drugs within solid lipid nanoparticles (SLNs). Methods and Materials: Isoniazid was selected as a representative hydrophilic drug with a high solubility of 230 mg/ml and a log P of -0.402 at 25°C (determined as per OECD TG 105 and 107 respectively). Three lipids/fatty acids (Glyceryl monostearate, Compritol 888 ATO® and stearic acid) were evaluated out of which Compritol 888 ATO® and stearic acid showed favorable interactions (FTIR and DSC studies) with isoniazid. The two lipids were used alone or in combination for preparing SLNs. Formulation of SLNs by microemulsification, method involved pouring the hot microemulsion into cold water under constant stirring, which may result in expulsion of the hydrophilic drug from the lipid matrix; hence, partitioning
of isoniazid from the hot lipid melts into cold water was also determined. Results and Discussion: Results indicate that combining stearic acid with Compritol 888 ATO® in certain ratio (1:4) led to significant entrapment efficiency (EE) of 84.0±1.1%. The formulations were subjected to morphological, physiochemical and in vitro drug release studies. Developed SLNs were found to be stable for 1 year at 4 °C. Conclusion: The study demonstrates the benefit of excipient screening techniques in improving entrapment efficiency of a hydrophilic drug.

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    ABSTRACT: Rifampicin (RIF), a vital constituent of antitubercular therapy, hydrolyze at the acidic pH of the stomach. The degradation is further enhanced by its interaction with Isoniazid (INH). Extent of RIF decomposition, in the presence and absence of INH, was determined at pH 1.2 (pH of empty stomach) at 37°C for 4h (maximum stomach residence time). Both the drugs decomposed at gastric pH (26.5% and 1.43% for RIF and INH respectively). Considering that solid lipid nanoparticles (SLNs) avert drug-drug interaction and also drug degradation, we incorporated RIF into SLNs. Latter reduced its degradation to ∼9% (from 26.50% when present alone) and to ∼20% (from 48.81% when INH was also present). Subsequent to this, we also incorporated INH into SLNs and the percent degradation of RIF in this combination (RIF SLNs+INH SLNs) further reduced to 12.35%. Furthermore, the degradation of INH in combination with RIF also reduced significantly from 13.2% to 2.7% when both the drugs were encapsulated individually within SLNs. Study therefore highlights the need to develop combinations of antitubercular drugs (ATDs) with caution and also establishes the usefulness of nanoparticulate technology to avoid drug-drug interaction.
    International Journal of Pharmaceutics 02/2013; · 3.99 Impact Factor

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May 22, 2014