Formulation development, in-vitro and ex-vivo evaluation of dry adsorbed solid lipid nanoparticles: an approach of overcoming olanzapine drawbacks

Abstract

Aim: The present study was aimed at preparing stable dry adsorbed nanoparticles (DANs) of olanzapine (OLZ) loaded solid lipid nanoparticles (SLNs) for sustained release.

Materials/methods: OLZ SLNs were prepared by hot melt emulsification and ultrasonication using Precirol ATO 5 (PRE) as a solid lipid, combination of Kolliphor ELP (KELP) and Tween 80 (T80) as surfactants, after optimising formulation and process variables. The SLN system was subjected to evaluation of particle size, zeta potential, entrapment efficiency (EE), in-vitro drug release and ex-vivo intestinal permeability studies using the chicken intestinal segments (jejunum). Further, these SLNs were converted into stable DANs by adsorbing onto a Neusilin US2 (NUS2) and Avicel CL 611 (ACL) carriers using the granulation-evaporative drying method. The DANs were characterised for redispersion properties, in-vitro drug release, thermal behaviour, crystallinity, and morphology.

Results: The SLN and DAN had a particle size of 238.0 nm [0.274 polydispersity index (PdI)] and 302.4 [0.494 PdI] respectively. The zeta potentials of SLN and DAN were found to be -29.3 mV and -26.3 mV, respectively. The SLN had 67% EE, and showed a sustained drug release in various media. The highest permeability of SLNs was observed in ex-vivo permeation model compared to the OLZ suspension, indicating that SLNs have the potential to bypass hepatic metabolism. The adsorption of SLNs onto carriers was confirmed by surface morphology. The DAN had good flow properties and sustained drug release similar to that of SLNs. The X-ray diffraction (XRD) patterns and endothermic peaks confirmed the complete encapsulation of actives in lipid matrices.

Conclusion: The encapsulating of OLZ in SLNs and converting it into DAN showed a sustained release and adsorption technique that can be used for improving the stability of NLC dispersion. The DANs can be offered in dosage forms such as filling into sachets, capsules and compressed into tablets.

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Materials

OLZ was kindly provided as a gift sample by K. C. Laboratories Pvt. Ltd., Gujarat. Precirol ATO 5 (PRE), Compritol ATO 888 (CMPR), Transcutol HP (THP), Labrasol (LBR), Plurol oleique (PLU) and Gelucire 50/13 (G50/13) were procured from Gattefosse, India. Glyceryl monstearate (GMS), stearic acid, palmitic acid and beeswax were obtained from Loba Chemie, India. Dynasan 114 (D114), Dynasan 116 (D116) and Dynasan 118 (D118) were obtained from Cremor, Germany. Tween 80 (T80), Kolliphor ELP (KELP), Kolliphor RH 40 (KRH40), Kolliphor P 188 (P188), Kolliphor P 407 (P407), Solutol HS 15 (SHS) and Kollidon CL SF (KCL) were kindly offered by BASF, India. Tween 20 (T20), Tween 40 (T40), Tween 60 (T60), Span 40 (S40) and Span 60 (S60) were provided by Mohini Organics, Mumbai. Neusilin US2 (NUS2), Neusilin UFL2 (NUFL)and Fujicalin SG (FUJ) were acquired from Gangwal Chemicals, Mumbai. FMC BioPolymer (India) supplied Avicel CL 611 (ACL), and Mammoths SPI Pharma supplied Mannitol (Pearlitol 100SD). Aerosil 200 (A200) and Aerosil R 972 (AR972) were obtained from Evonik (India), Anhydrous Lactose (SuperTab 21AN) was obtained from DFE Pharma (India) and Syloid 244 FP (S44FP) was gifted by Grace Davison chemicals. All other reagents and chemicals used in this study were of analytical grade.

Source: Rajashree Hirlekar, Alfiha Momin, Srinivas Bhairy, “Formulation development, in-vitro and ex-vivo evaluation of dry adsorbed solid lipid nanoparticles”, Eur. Pharm. J. 2024, AoP, 1-15, ISSN 1338-6786 (online) and ISSN 2453-6725 (print version), DOI: 10.2478/afpuc-2024-0004.

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