Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability.

Shweta Gupta,Ambikanandan Misra,Abdelwahab Omri,Rajesh Kesarla,Narendra Chotai

doi:10.1155/2017/5984014

Abstract

The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles were prepared by high pressure homogenization technique using a systematic approach of design of experiments (DoE) and evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be −21.2 mV and the formulation was found stable. The in-vivo pharmacokinetic studies revealed increased concentration of the drug in brain, as desired, when administered through intranasal route indicating its potential for an attempt towards complete eradication of HIV and cure of HIV-infected patients.

Highlights

According to the World Health Organization, approximately 35 million people worldwide are living with HIV/AIDS including 3.2 million children of less than 15 years age
Pharmaceutical development should include defining of quality target product profile (QTPP), identifying and determining potential critical quality attributes (CQAs), selecting an appropriate manufacturing process, defining a control strategy, and identifying through, for example, prior knowledge, experimentation, and risk assessment, the material attributes, and process parameters that can have an effect on product CQAs
A CQA is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality [43, 44]

Summary

Introduction

According to the World Health Organization, approximately 35 million people worldwide are living with HIV/AIDS including 3.2 million children of less than 15 years age. AIDS is the sixth leading cause of death among people aged 25–44 in the United States [2]. Due to the restricted entry of anti-HIV drugs, the brain is thought to form a viral sanctuary site. This results in virological resistance, and is often associated with the development of complications such as progressive deterioration in mental function, symptoms of motor abnormalities, mild neurocognitive disorder (MDR), HIV associated dementia (HAD), HIV encephalitis (HIVE), and even death in many cases [3,4,5,6]

Methods

Results

Conclusion