A Method to Prepare Solid Lipid Nanoparticles with Improved Entrapment Efficiency of Hydrophilic Drugs

Current Nanoscience (Impact Factor: 1.1). 04/2013; 9(2):211-220. DOI: 10.2174/1573413711309020008


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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Available from: Indu Pal Kaur
    • "Another reason for higher diffusion of RHT in case of SLN could be either formation of amorphous dispersion or solubilization of RHT in Compritol matrix as revealed from DSC and XRD data as shown in Fig. 6B. In general the solubility increases with increase in amorphicity and hence higher release was obtained with SLN, which was not in case of drug solution (Rohit and Pal, 2013). RHT SLN exhibited highest R 2 value (0.9949) for Higuchi model. "
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    ABSTRACT: In the present investigation, Quality by Design (QbD) approach was applied on the development and optimization of solid lipid nanoparticle (SLN) formulation of hydrophilic drug rivastigmine (RHT). RHT SLN were formulated by homogenization and ultrasonication method using Compritol 888 ATO, tween-80 and poloxamer-188 as lipid, surfactant and stabilizer respectively. The effect of independent variables (X1 - drug: lipid ratio, X2 - surfactant concentration and X3 - homogenization time) on quality attributes of SLN i.e. dependent variables (Y1 - size, Y2 - PDI and Y3 -%entrapment efficiency (%EE)) were investigated using 3(3) factorial design. Multiple linear regression analysis and ANOVA were employed to indentify and estimate the main effect, 2FI, quadratic and cubic effect. Optimized RHT SLN formula was derived from an overlay plot on which further effect of probe sonication was evaluated. Final RHT SLN showed narrow size distribution (PDI- 0.132 ± 0.016) with particle size of 82.5 ± 4.07 nm and%EE of 66.84 ± 2.49. DSC and XRD study showed incorporation of RHT into imperfect crystal lattice of Compritol 888 ATO. In comparison to RHT solution, RHT SLN showed higher in-vitro and ex-vivo diffusion. The diffusion followed Higuchi model indicating drug diffusion from the lipid matrix due to erosion. Histopathology study showed intact nasal mucosa with RHT SLN indicating safety of RHT SLN for intranasal administration. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Jul 2015 · European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences
    • "Low aqueous volumes were achieved by diluting the microemulsion with a very small (equal) volume of cold water than normally proposed 1:10 or 1:25 dilution with cold water. Former concept has been developed and reported by us for the first time (Kaur and Bhandari, 2012; Kaur and Singh, 2013). Low aqueous volume is expected to prevent drug expulsion while the (Kumar et al., 2013), high loading will allow administration of the required dose in smaller volumes. "
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    ABSTRACT: Rifampicin (RIF) was encapsulated into solid lipid nanoparticles (SLNs) to overcome its poor and unreliable oral bioavailability. Novel microemulsification method with high drug loading (50%) and entrapment efficiency (�67%) was developed (Indian Patent Application 3356/DEL/2013). RIF-SLNs were characterized using TEM, AFM, DSC and XRD. Near neutral SLNs (zeta �3.5 � 0.8), with average particle size of 130.0 � 22.6 nm showed 70.12% release in phosphate buffer pH 6.8 in 9 days. Single oral dose (50 mg/kg) pharmacokinetic studies in Wistar rats indicated 8.14 times higher (in comparison to free RIF) plasma bioavailability with sustained levels for 5 days. Pharmacodynamic parameters viz. TMIC (120 h; time for which plasma levels were above MIC of 0.2 mg/ml), AUC0–1/MIC (1868.9 h) and Cmax/MIC (75.6) for RIF-SLNs were greater than free RIF by 2.5, 8.2 and 6.6 times, respectively. Similar LD50 (1570 mg/kg) and absence (or reversal in satellite group) of adverse events in repeat dose (three doses; highest dose was up to 50 times the human therapeutic dose) toxicity studies confirmed safety of RIF-SLNs. Improved pharmacokinetic profile of RIF-SLNs can be translated to a reduced dose and dosage frequency of RIF, thus resulting in lower or no hepatotoxicity commonly associated with its use
    No preview · Article · May 2015 · International Journal of Pharmaceutics
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    • "Moreover, SLN have proven in previous studies to have a positive effect on increasing the activity of some water-soluble drugs (Shah et al., 2012). It was also reported that SLN could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release for water-soluble active compounds (Gandomi et al., 2012; Rohit and Pal, 2013). "

    Full-text · Article · Sep 2014 · Zeitschrift fur Naturforschung. C, Journal of biosciences
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