Solubility Of Efavirenz Research Articles

Using natural excipients to enhance the solubility of the poorly water-soluble antiretroviral, efavirenz

The anti-retroviral drug efavirenz (EFV) exhibits poor aqueous solubility which renders pharmaceutical formulation challenging. During a pre-formulation phase, involving spray drying of EFV for pediatric dosage form development, the combination of EFV with two natural excipients, pea protein isolate (PPI) and inulin (IN), was explored. In this study the effect of PPI and IN on the solubility of EFV became apparent, leading to an in-depth investigation. Equilibrium solubility studies were performed for different combinations of EFV, PPI, and IN in distilled water and buffered solutions in the presence and absence of commonly used surfactants, Tween® 20 and sodium lauryl sulfate (SLS). In the combination of EFV and PPI, PPI significantly improved EFV solubility while in the combination of EFV and IN, EFV solubility was not affected significantly. In the combination of EFV, PPI, and IN, a significant solubility improvement was noted, yet the degree of solubility improvement was less compared to the combination of only EFV and PPI. Further, the effects of PPI and IN on the solubility prove to be concentration-related. It was concluded that PPI can be used as a functional excipient to improve EFV solubility, conversely IN can be used as a drug dissolution retardant, and finally it was also concluded that it is crucial to optimize the ratio of drug to excipient to ensure optimal pharmaceutical formulation outcomes.

Preparation and characterization of efavirenz cocrystals: An endeavor to improve the physicochemical parameters

Cocrystallization technique has gained increasing interest due to its ability to modify the physicochemical properties of a drug substance. Efavirenz comes under biopharmaceutical classification system class II compounds that denote the low solubility and high permeability nature of the drug. Thus, the main aim of this study is to develop efavirenz cocrystals using different coformers other than previously reported to enhance the dissolution behavior and solubility of efavirenz. Further, to draw a meaningful conclusion about selecting the coformers to synthesize the cocrystals. The cocrystals of efavirenz with four different water soluble coformers such as DL-alanine, oxalic acid, maleic acid, and nicotinamide (1:1 molar ratio) were prepared using slow solvent evaporation strategy. The cocrystals characterization was done using FT-IR, DSC, PXRD and SEM. Further, the stability, solubility and dissolution studies were performed along with fitting the dissolution data into kinetic models. The FT-IR data revealed the negligible shift in –C=O and –N-H/-O-H stretching frequencies in prepared cocrystals compared to a pure drug. However, the thermal behavior of prepared cocrystals showed the strong interactions between pure drug and coformers indicating the existence of hydrogen bond between drug and coformer. The PXRD patterns of cocrystals indicated different 2ϴ values compared to their starting materials. Although all the coformers are water soluble, the increased dissolution profile was seen only for efavirenz-DL-alanine and efavirenz-oxalic acid cocrystal, whereas efavirenz-maleic acid and efavirenz-nicotinamide cocrystals exhibited decreased dissolution compared to pure efavirenz. Nevertheless, the cocrystals were found to be stable for at least six months in ambient conditions. This concludes that cocrystallization is an apt strategy to improve the physicochemical properties of an active pharmaceutical ingredient only with suitable coformers.

Inclusion Compound of Efavirenz and γ-Cyclodextrin: Solid State Studies and Effect on Solubility.

Efavirenz is an antiretroviral drug of widespread use in the management of infections with human immunodeficiency virus type 1 (HIV-1). Efavirenz is also used in paediatrics, but due to its very poor aqueous solubility the liquid formulations available resort to oil-based excipients. In this report we describe the interaction of γ-cyclodextrin with efavirenz in solution and in the solid state. In aqueous solution, the preferential host–guest stoichiometry was determined by the continuous variation method using 1H NMR, which indicated a 3:2 host-to-guest proportion. Following, the solid inclusion compound was prepared at different stoichiometries by co-dissolution and freeze-drying. Solid-state characterisation of the products using FT-IR, 13C{1H} CP-MAS NMR, thermogravimetry, and X-ray powder diffraction has confirmed that the 3:2 stoichiometry is the adequate starting condition to isolate a solid inclusion compound in the pure form. The effect of γ-cyclodextrin on the solubility of efavirenz is studied by the isotherm method.

SOLUBILITY ENHANCEMENT OF EFAVIRENZ (BCS CLASS II DRUG) BY CYCLODEXTRIN INCLUSION COMPLEX TECHNIQUE

The solubility of BCS class II drugs can be enhanced using inclusion complex techniques. Cyclodextrin (CD) and its derivatives are promising carrier for the enhancement of aqueous solubility of drugs. The use of the Kneading technique to obtain solid inclusion system permitted the formation of a uniform, substantially non-crystalline particle, which increased the solubility and stability of Efavirenz (EFV). The present work shows the enhancement of aqueous solubility of BCS class II drug i.e. EFV by making inclusion complex with I²-CD. The aqueous solubility of EFV is calculated to be 5± 0.003 µg/ml which was increased up to 288.9±0.005 µg/ml when complexed with I²-CD in ratio of 1:1 and 318.5± 0.03 µg/ml in ratio of 1:2. This shows that, the inclusion complex technique is a promising way to enhance aqueous solubility.

Design of a novel crosslinked HEC-PAA porous hydrogel composite for dissolution rate and solubility enhancement of efavirenz

The purpose of this research was to synthesize, characterize and evaluate a Crosslinked Hydrogel Composite (CHC) as a new carrier for improving the solubility of the anti-HIV drug, efavirenz. The CHC was prepared by physical blending of hydroxyethylcellulose (HEC) with poly(acrylic acid) (PAA) (1:1) in the presence of poly(vinyl alcohol) (PVA) (as a crosslinker) (1:5) under lyophilization. Efavirenz was loaded in situ into the CHC in varying proportions (200–600mg). The CHC demonstrated impressive rheological properties (dynamic viscosity=6053mPa; 500s−1) and tensile strength (2.5mPa) compared with the native polymers (HEC and PAA). The physicochemical and thermal behavior also confirmed that the CHC was compatible with efavirenz. The incorporation of efavirenz in the CHC increased the surface area (4.4489–8.4948m2/g) and pore volume (469.547–776.916Å) of the hydrogel system which was confirmed by SEM imagery and BET surface area measurements. The solubility of efavirenz was significantly enhanced (150 times) in a sustained release manner over 24h as affirmed by the in vitro drug release studies. The hydration medium provided by the CHC network played a pivotal role in improving the efavirenz solubility via increasing hydrogen bonding as proved by the zeta potential measurements (−18.0 to +0.10). The CHC may be a promising alternative as an oral formulation for the delivery of efavirenz with enhanced solubility.

Development and characterization of taste masked Efavirenz pellets utilizing hot melt extrusion

The objective of this study was to formulate taste-masked pellets of Efavirenz (EFZ) with Eudragit E PO as the matrix polymer utilizing hot melt extrusion (HME) technology. The drug/polymer physical mixtures were extruded as rods with a co-rotating twin-screw extruder and then pelletized. The chemical interaction between EFZ and Eudragit E PO was determined using Fourier transform infrared (FTIR) spectroscopy. Solid-state characterization of EFZ in the Eudragit E PO matrix was carried out using differential scanning calorimetry (DSC), Powder X-ray Diffraction (PXRD) and Scanning electron microscopy (SEM) techniques. The solubility of EFZ was improved significantly due to its conversion into a more water-soluble amorphous form. Drug load had a significant effect on EFZ release characteristics from the pellets. In vitro release profiles obtained with the extruded pellets at pH 6.8 (simulated salivary medium) indicated that EFZ release would be extremely limited in the saliva, unlike the physical mixture, thus avoiding irritation of the oral mucosa (BMS, burning mouth syndrome). More than 90% drug release in 30minutes was observed in simulated gastric medium (pH 1.2) with the extruded pellets. The dissolution rate of EFZ from the melt extruded pellets was faster than that from thephysical mixtures at all drug loads (p