Tacrolimus-loaded nanostructured lipid carriers for oral delivery-in vivo bioavailability enhancement

Abstract Atazanavir (ATV) is widely used as anti-HIV agent with poor aqueous solubility which requires fabrication of novel drug delivery system to enhance therapeutic activity and safety. For this purpose, the quality by design (QbD) based ATV loaded nanostructured lipid carriers (NLCs) to address the challenges of bioavailability and its safety on oral administration. Herein, the main objective was to identify the influencing variables for the production of quality product. Considering this objective, quality target product profile (QTPP) was assigned and a systematic risk assessment study was performed to identify the critical material attributes (CMAs) and critical process parameter (CPP) having an influence on critical quality attributes (CQAs). Lipid concentrations, surfactant concentrations, and pressure of high-pressure homogenizer were identified as CMAs and CPP. ATV-NLCs were prepared by emulsification-high pressure homogenization method and further lyophilized to obtain solid-state NLCs. The effect of formulation variables (CMAs and CPP) on responses like particle size (Y1), polydispersity index (Y2), and zeta potential (Y3) was observed by central composite rotatable design (CCRD). The data were statistically evaluated by ANOVA for confirmation of a significant level (P<0.05). The optimal conditions of NLCs were obtained by generating design space and desirability value. The lyophilized ATV-NLCs were characterized by DSC, PXRD, and FT-IR analysis. The morphology of NLCs was revealed by TEM and FESEM. In vitro study suggested a sustained release pattern of drug (92.37±1.03 %) with a mechanism of Korsmeyer-Peppas model (r2 =0.925, and n=0.63). In vivo evaluation in Wistar rats showed significantly higher (p<0.001) plasma drug concentration of ATV-NLCs as compared to ATV-suspension using chylomicron flow block model. The relative bioavailability of ATV-NLCs was obtained to be 2.54 folds. Thus, a safe and promising drug targeting system was successfully developed to improve bioavailability and avoiding first-pass effect ensures to circumvent the acute-toxicity of liver.

Download Full-text

Nanostructured lipid carriers for oral delivery of baicalin: In vitro and in vivo evaluation

Colloids and Surfaces A Physicochemical and Engineering Aspects ◽

10.1016/j.colsurfa.2014.11.015 ◽

2015 ◽

Vol 466 ◽

pp. 154-159 ◽

Cited By ~ 42

Author(s):

Jingjing Luan ◽

Fang Zheng ◽

Xiaoye Yang ◽

Aihua Yu ◽

Guangxi Zhai

Keyword(s):

Oral Delivery ◽

Nanostructured Lipid Carriers ◽

In Vivo Evaluation

Download Full-text

Improved oral bioavailability of docetaxel by nanostructured lipid carriers: in vitro characteristics, in vivo evaluation and intestinal transport studies

RSC Advances ◽

10.1039/c5ra14588k ◽

2015 ◽

Vol 5 (117) ◽

pp. 96437-96447 ◽

Cited By ~ 21

Author(s):

Guihua Fang ◽

Bo Tang ◽

Yanhui Chao ◽

Yu Zhang ◽

Hui Xu ◽

...

Keyword(s):

Oral Bioavailability ◽

Oral Delivery ◽

Intestinal Transport ◽

Nanostructured Lipid Carriers ◽

Absorption Mechanism ◽

In Vivo Evaluation ◽

Transport Studies

The objective of the current study was to explore the potential of nanostructured lipid carriers (NLC) for oral delivery of docetaxel (DTX) and investigate the absorption mechanismin vivo.

Download Full-text

Nanostructured lipid carriers- A versatile carrier for oral delivery of lipophilic drugs

Recent Patents on Nanotechnology ◽

10.2174/1872210514666200909154959 ◽

2020 ◽

Vol 14 ◽

Author(s):

Priyanshi Patel ◽

Mitali Patel

Keyword(s):

Oral Bioavailability ◽

Oral Delivery ◽

Water Solubility ◽

Oral Formulation ◽

Lipid Nanoparticles ◽

Nanostructured Lipid Carriers ◽

Lipophilic Drugs ◽

Promising Tool ◽

Pharmaceutical Industries

Background: Around 40% of newly discovered chemical entities in pharmaceutical industries have poor water solubility and hence they suffer from low oral bioavailability owing to undesirable physicochemical and pharmacokinetic properties. So, it is the challenge for the formulation scientists to develop the oral formulation that can mitigate the pitfalls associated with such lipophilic drugs. Methods: Lipid nanoparticles hold a promising tool to augment the pitfalls of lipophilic drugs as lipid component can effectively increases the absorption of drugs which leads to improvement in oral bioavailability. They are also considered as safe because they are made up of physiological lipids which are biocompatible and biodegradable in nature. Amongst the lipid nanoparticles, Nanostructured lipid carriers (NLCs) are the second-generation lipid nanoparticle and were developed to conquer the limitations of solid lipid nanoparticles. They increase the solubility, permeability, reduce metabolism, P-glycoprotein efflux and thereby increase the bioavailability of poorly soluble drugs. Conclusion: This review highlights the various aspects of NLCs such as formulation components, types, in vivo fate, Pharmacokinetic, toxicity, recent advances and patent review of NLCs in drug delivery.

Download Full-text

Formulation design, characterization, and in vitro and in vivo evaluation of nanostructured lipid carriers containing a bile salt for oral delivery of gypenosides

International Journal of Nanomedicine ◽

10.2147/ijn.s194934 ◽

2019 ◽

Vol Volume 14 ◽

pp. 2267-2280 ◽

Cited By ~ 4

Author(s):

Gang Yang ◽

Feihua Wu ◽

Minyan Chen ◽

Jian Jin ◽

Rong Wang ◽

...

Keyword(s):

Bile Salt ◽

Oral Delivery ◽

Nanostructured Lipid Carriers ◽

In Vivo Evaluation ◽

Formulation Design

Download Full-text

FORMULATION AND EVALUATION OF OPTIMISED MALTODEXTRIN BASED PRONIOSOME POWDERS CONTAINING BAZEDOXIFENE ACETATE FOR ORAL DELIVERY

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2020v12i6.40285 ◽

2020 ◽

pp. 56-66

Author(s):

SMITHA GANDRA

Keyword(s):

Oral Bioavailability ◽

Oral Delivery ◽

Ex Vivo ◽

In Vivo Studies ◽

In Vitro Dissolution ◽

Ionic Surfactant ◽

Bioavailability Enhancement ◽

Cholesterol Ratio

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of bazedoxifene acetate by improving solubility, dissolution and/or intestinal permeability. Methods: Proniosomal powder formulations were prepared with bazedoxifene acetate drug varying the span 40 and cholesterol ratio in the range of 0.8:0.2 to 0.2:0.8 using maltodextrin as a carrier by slurry method. The prepared proniosomal powder was filled into capsules. The bioavailability enhancement of proniosomes loaded with drug was studied focusing on non-ionic surfactants composition and drug: span 40 ratio. Prepared proniosomes were characterized for their particle size distribution, zeta potential, entrapment efficiency, in vitro dissolution study and thermal characteristics to understand the phase transition behavior. Further, the formulated proniosomes were subjected to stability behavior, ex vivo permeation studies using rat intestine followed by in vivo studies. Results: Physico-chemical studies help in the optimization of formulations. Enhancement in dissolution is due to the incorporation of bazedoxifene acetate into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Ex vivo studies show significant permeation enhancement across the gastrointestinal membrane compared to control. Conclusion: In conclusion, proniosomes provide a powerful and functional way of the distribution of inadequately soluble bazedoxifene acetate drug, which is proved from in vivo studies based on the enhanced oral delivery.

Download Full-text

ROSUVASTATIN CALCIUM PRONIOSOME POWDER: A NOVEL APPROACH TO IMPROVE INTESTINAL ABSORPTION AND BIOAVAILABILITY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2020.v13i12.39585 ◽

2020 ◽

pp. 148-156

Author(s):

SMITHA GANDRA

Keyword(s):

Oral Bioavailability ◽

Oral Delivery ◽

Ex Vivo ◽

In Vivo Studies ◽

In Vitro Dissolution ◽

Ionic Surfactant ◽

Bioavailability Enhancement ◽

Rosuvastatin Calcium

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of rosuvastatin calcium by improving solubility, dissolution, and/or intestinal permeability. Methods: Proniosomal powder formulations were prepared with rosuvastatin calcium drug varying the Span 40 and cholesterol ratio in the range of 0.8:0.2–0.2:0.8 using maltodextrin as carrier by slurry method. The prepared proniosomal powder was filled into capsules. The bioavailability enhancement of proniosomes loaded with drug was studied focusing on non-ionic surfactants composition and drug:Span 40 ratio. Prepared proniosomes were characterized for their particle size distribution, zeta potential, entrapment efficiency, in vitro dissolution study, and thermal characteristics to understand the phase transition behavior. Further, the formulated proniosomes were subjected to stability behavior, ex vivo permeation studies using rat intestine followed by in vivo studies. Results: Physicochemical studies help in optimization of formulations. Enhancement in dissolution is due to incorporation of rosuvastatin calcium into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Ex vivo studies show significant permeation enhancement across gastrointestinal membrane compared to control. Conclusion: Proniosomes provide a powerful and functional way of distribution of inadequately soluble rosuvastatin calcium drug which is proved from in vivo studies based on the enhanced oral delivery.

Download Full-text