This st�dy describes a 3 2 f�ll factorial experimental design to optimize the form�lation of dithranol (DTH) loaded solid lipid nanoparticles (SLN) by the pre�em�lsion �ltrasonication method. The variables dr�g� lipid ratio and sonication time were st�died at three levels and arranged in a 3 2 factorial design to st�dy the infl�ence on the response variables particle size and % entrapment efficiency (%��). From the statistical analysis of data polynomial eq�ations were generated. The particle size and %�� for the 9 batches (R1 to R9) showed a wide variation of 219�348 nm and 51.33� 71.8� %, respectively. The physical characteristics of DTH�loaded SLN were eval�ated �sing a particle size analyzer, differential scanning calorimetry and X�ray diffraction. The res�lts of the optimized form�lation showed an average particle size of 219 nm and entrapment efficiency of 69.88 %. Ex-vivo dr�g penetration �sing rat skin showed abo�t a 2�fold increase in localization of DTH in skin as compared to the marketed preparation of DTH.Uniterms: Solid lipid nanoparticles. Homogenization. Ultrasonication. 3 2 factorial design. Dithranol.�ste est�do descreve o planejamento factorial 3 2 para otimizar a form�lação de nanopartíc�las lipídicas sólidas (SLN) carregadas com ditranol (DTH) pelo método da �ltrassonificação pré�em�lsão. As variáveis como proporção de fármaco�lipídio e o tempo de sonicação foram est�dados em três níveis e arranjados em planejamento fatorial 3 2 para est�dar a infl�ência nas variáveis de resposta tamanho de partíc�la e eficiência percent�al de retenção do fármaco (%��). Pela análise estatística, geraram�se eq�ações polinomiais. O tamanho da partíc�la e a %�� para os 9 lotes (R1 a R9) mostraram ampla variação, respectivamente, 219�348 nm e 51,33�71,8�%. As características físicas das SLN carregadas com DTN foram avaliadas �tilizando�se analisador de tamanho de partíc�la, calorimetria de varred�ra diferencial e difração de raios X. Os res�ltados da form�lação otimizada mostraram tamanho médio de partíc�la de 219 nm e eficiência de retenção do fármaco de 69,88%. A penetração ex vivo do fármaco �tilizando pele de rato mostro� a�mento de, aproximadamente, d�as vezes na localização de DTH na pele, comparativamente à preparação de DTH comercializada.Unitermos: Nanopartíc�las lipídicas sólidas. Homogeneização. Ultrasonicação. Planejamento fatorial. Ditranol.

Atorvastatin is a synthetic statin commonly used in the treatment of hypercholesterolemia. Apart from this, statins appear to have pleiotropic effects, including modulation of cell growth, apoptosis. Through modulation of these pathways, statins have the potential to influence a wide range of disease processes, including cancer. However, poor aqueous solubility (0.1 mg/mL) and poor oral bioavailability has limited therapeutic application of atorvastatin. Present work is an attempt to improve tumor targeting of atorvastatin by incorporating in nanostructured lipid carriers (NLCs) and studying its anticancer activity on MCF-7 cell lines. NLCs of atorvastatin were formulated by high-speed homogenization followed by probe sonication method. The optimized batch of NLCs had a mean size of 130.02 ± 3.1 nm and entrapment efficiency of 90.42 ± 3.7%. The in vitro drug release study by dialysis method indicated that drug entrapped in the NLCs remains entrapped at acidic pH as well as in phosphate buffer of pH 7.4 for a prolonged period of time as compared to plain drug. In vitro cytotoxicity studies on MCF-7 (mammary adenocarcinoma human cell lines) cell lines showed that concentration of drug required for total growth inhibition (TGI) and 50% growth inhibition (GI50) of MCF-7 cells was found to be 27.4 µg/mL and <10 µg/mL respectively, in case of atorvastatin- NLCs which is less than that required in case of plain atorvastatin and almost similar to that of adriamycin. All these findings reinforce the fact that atorvastatin loaded NLCs are promising novel delivery system for treating breast cancer.

Background: Mirabegron (MBN), a β-3 adrenergic agent, is used in the treatment of overactive bladder. MBN has alow water solubility, high first-pass metabolism, and low bioavailability, consequently, having poor absorption in the gastrointestinal tract. Objective: The present study is intended at formulating Mirabegron-loaded solid lipid nanoparticles (MBN-SLN) coated with PEG-400 to bypass hepatic first-pass metabolism and to improve its oral bioavailability. Methods: MBN-SLNs were developed using glyceryl monostearate by pre-emulsion- ultrasonication method which was then optimized applying Box-Behnken Design. The optimized batch of MBN-SLN was selected for surface-modification with PEG-400 (MBN-PEG-SLN) and characterized by photon correlation spectroscopy, DSC, and XRD. Bioavailability studies were conducted in Wistar rats after oral administration of plain MBN dispersion, MBN-SLN, and MBN-PEG-SLN. Results: Stable MBN-SLNs and MBN-PEG-SLN of the optimized batch having a mean particle size of 162.7 nm and 149.9 nm; Zeta potential of -39.1 mV and -30.9 mV; %entrapment of 89.90% and 90.12%, respectively, were developed. The results of the in-vitro drug release studies demonstrated a significant slow release of MBN from MBN-SLN (69.38%) and MBN-PEG-SLN (61.33%) as compared to the dispersion of pure drug (92.10%). The relative bioavailability, as a result of the invivostudies, of MBN from MBN-PEG-SLN increased by 2-fold, based on the Cmax values, in comparison with the plain MBN dispersion. Conclusion: Thus, the study established that the oral bioavailability of MBN could be improved by the administration of MBN-PEG-SLN. The obtained results indicate SLNs as a potential drug delivery system for improving the bioavailability of poorly bioavailable drugs such as MBN by abating the first-pass metabolism.

Background: Dronedarone HCl (DRD), owing to its poor aqueous solubility and extensive presystemic metabolism shows low oral bioavailability of about 4% without food, which increases to approximately 15% when administered with a high fat meal. Objective: Solid lipid nanoparticles (SLN) were designed with glyceryl monstearate (GMS) in order to improve oral bioavailability of DRD. Methods: Hot homogenization followed by probe sonication was used to prepare SLN dispersions. Box-Behnken design was used to optimize manufacturing conditions. SLN were characterized for particle size, zeta potential, entrapment efficiency, physical state and in vitro drug release. Pharmacokinetics and intestinal uptake study of dronedarone HCl loaded solid lipid nanoparticles (DRD-SLN) in the presence and absence of endocytic uptake inhibitor, chlorpromazine (CPZ) was performed with conscious male Wistar rats. Results: Optimized formulation of SLN showed particle size of 233 ± 42 nm and entrapment efficiency of 87.4 ± 1.29%. Results of pharmacokinetic studies revealed enhancement of bioavailability of DRD by 2.68 folds from SLN as compared to DRD suspension. Significantly reduced bioavailability of DRD-SLNs in the presence of chlorpromazine, demonstrated the role of endocytosis in uptake of SLN formulation. Conclusion: These results indicated that dronedarone HCl loaded SLN could potentially be exploited as a delivery system for improving oral bioavailability by minimizing first pass metabolism.

Sertraline hydrochloride is an antidepressant with limited bioavailability and solid lipid nanoparticles (SLN) is one of the approaches to improve bioavailability. This study describes a box behnken experimental design to optimize the formulation of sertraline hydrochloride loaded solid lipid nanoparticles (SLN) by the probe sonication method. For optimization, a three factors and two levels box-behnken design was applied to study the effect of independent variables (factors) i.e. drug to lipid ratio (X 1), surfactant concentration (X 2) and probe sonication time (X 3) on dependent variables (responses) i.e. particles size (Y 1), entrapment efficiency (Y 2). Polynomial equations were generated on the basis of statistical analysis of data. The particle size and % EE for the 13 batches (R 1 to R 13) showed a wide variation of 145-201 nm and 80.5-88.8 %, respectively. The physical characteristics of sertraline hydrochloride loaded SLN were evaluated using FT-IR, differential scanning calorimetry and X-ray diffraction. The results of the optimized formulation showed an average particle size of 130.6 nm and entrapment efficiency of 85.30 %.