Tablet Formulation and Enhancement of Aqueous Solubility of Efavirenz by Solvent Evaporation Co-Crystal Technique (original) (raw)
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Materials science & engineering. C, Materials for biological applications, 2017
Poor aqueous solubility of drugs has emerged as a major issue for pharmaceutical scientists from many decades. The current study explores the manufacture and development of a thermodynamically stabilized solid crystal suspension (SCS) of poorly water soluble drug efavirenz via hot melt extrusion. Efavirenz is a non-nucleoside reverse transcriptase inhibitor and belongs to BCS class II. The SCS was prepared using pearlitol and xylitol as a crystalline carrier. The drug-excipient blend was processed by hot melt extrusion with up to 50% (w/w) drug loading. Physico-chemical characterization of the SCS conducted via a scanning electron microscopy, differential scanning calorimetry and hot stage microscopy confirmed that SCS are in crystalline state. Similarly, X-ray powder diffraction analysis revealed highly crystalline existence of pure drug, crystalline carriers and developed SCS. The FTIR chemical imaging analysis of SCS formulations showed a homogeneous drug distribution within resp...
Formulation and development of bicontinuous nanostructured liquid crystalline particles of efavirenz
Colloids and Surfaces B: Biointerfaces, 2015
Efavirenz is a lipophilic non-nucleoside reverse transcriptase inhibitor used in the first-line pediatric therapeutic cocktail. Due to its high lipophilicity (log P = 5.4) and poor aqueous solubility (intrinsic water solubility = 8.3 μg/ml) efavirenz has low bioavailability. A 30 mg/ml solution in a medium-chain triglyceride vehicle is the only pediatric formulation available with an oral bioavailability 20% lower than the solid form. The current work was aimed at formulating and characterizing liquid crystal nanoparticles for oral delivery of efavirenz to improve oral bioavailability, provide sustained release, minimize side effects and drug resistance. Formulation of cubosomes was done by two methods; sonication and spray drying. Sonication gave highest entrapment efficiency and least particle size. Further, monoolein was substituted with phytantriol as monoolein gets degraded in the presence of lipase when administered orally with consequent loss of liquid crystalline structure. It was confirmed that there was no difference in particle size, entrapment efficiency and nature of product formed by using monoolein or phytantriol. The best formulation was found to be F9, having particle size 104.19±0.21 nm and entrapment efficiency 91.40±0.10 %. In-vitro release at the end of 12 hrs was found to be 56.45% and zeta potential to be-23.14 mV which stabilized the cubic phase dispersions. It was further characterized for TEM, small angle X-ray scattering (SAXS), DSC and stability studies. SAXS revealed Pn3m space group, indicating a diamond cubic phase which was further confirmed by TEM. Pharmacokinetics of EFV was studied in male Wistar rats. EFV-loaded cubosome dispersions exhibited 1.93 and 1.62-fold increase in peak plasma concentration (C max) and 1.48 and 1.42-fold increase in AUC in comparison to that of a suspension prepared with the contents of EFV capsules suspended in 1.5% carboxymethylcellulose PBS solution (pH 5.0), and an EFV solution in medium-chain triglyceride respectively.Thus, stable cubosomes of efavirenz with increased bioavailability providing sustained release effect could be prepared successfully using phytantriol and poloxamer 407.
A Brief Review On Pharmaceutical Co-crystals
2021
Recent studies has found that, discovering and developing novel medications is insufficient to attain therapeutic excellence and gain market economies. As a result, changed formulations of currently available medications are getting more significant. Also, poor water solubility and inadequate bioavailability of an active medicinal ingredient are two factors that limit the growth of a new product. The pharmacological action of the pharmaceutically active ingredient is unaffected by co-crystallization, with pharmaceutically acceptable molecules, although it can improve physical qualities such as solubility, stability and rate of dissolution. Most importantly, it is possible to use co-crystal to generate novel pharmaceuticals with improved solubility, improving treatment efficiency and safety. The most significant factor in the production of co-crystal is thermodynamic stability. Co-crystal formation can be performed by Grinding Methods, Spray Drying Method, Solvent Evaporation Techniq...
A Study on Solubility Enhancement of Etravirine by Crystal Engineering Method
Indian Journal of Pharmaceutical Sciences, 2022
Bhattacharyya et al.: Crystal Engineering of Etravirine for Solubility Enhancement Etravirine, an antiretroviral agent, used in the treatment of human immunodeficiency virus belongs to biopharmaceutical classification system classification IV. The reported solubility of the drug is 0.0169 mg/ ml. In the present study, an attempt was made to enhance the solubility of etravirine by crystal engineering technique. The cocrystallization method was carried out using 12 different coformers and each coformer was studied in two different stoichiometric ratios. A preliminary screening of all the cocrystals was done by determination of melting point and solubility. A statistical evaluation of all the cocrystals on solubility was carried out at a significance level of p<0.05. The best cocrystals were subjected to drug content, in vitro drug release, solid-state study (fourier transform infrared spectroscopy, differential scanning calorimetry, powder x-ray diffraction) and stability study for 3 mo. Coformer benzoic acid showed a significant improvement in etravirine solubility in the drug:coformer ratio of 1:1 and 1:2. The drug:benzoic acid ratio of 1:2 was found to have more solubility and showed enhanced dissolution compared to pure drug. The in vitro dissolution rate of the drug:benzoic acid ratio of 1:2 was found to be more than 90 % in 60 min. Therefore, it can be concluded that the cocrystallization method with benzoic acid as coformer can be a promising approach for solubility improvement of etravirine.
Pharmaceutical Co-crystal : An Emerging Technique to enhance Physicochemical properties of drugs
International Journal of ChemTech Research, 2020
Major constraints in development of new product are poor aqueous solubility, stability and low oral bioavailability, low permeability. As majority of drugs marketed worldwide are administered by oral route and about 40% -50% of the new molecular entities were never invade into the market because of such biopharmaceutical issues.So issues related to poor physiochemical property of an active pharmaceutical ingredient (API) can be resolved using cocrystallization approach.Crystallization emerge as potential technique for enhancement of solubility of poorly aqueous soluble drugs also helps to improve physicochemical with preserving the pharmacological properties of the API . Cocrystals are solids that are crystalline single-phase materials composed of two or more different molecular and/or ionic compounds generally in a stoichiometric ratio which are neither solvates/hydrates nor simple salts. It is multicomponent system in which one component is API and another is called coformer. Cofo...
The aim of the work was to improve the dissolution properties of the poorly soluble drug, Efaverinz by the liquisolid compaction technique. The study demonstrated with confidence that the liquisolid technique is promising approach for improvement of solubility of poorly soluble drugs. In vitro drug release of Efaverinz compacts showed increase in dissolution rate of Efaverinz. So PEG 400, PG, Tween 80 could be economic substitute as dissolution enhancing agent. Stability studies showed that there were no significant changes in physical and chemical properties of formulation F5 after 2 months. Propylene glycol in 1:0.25 ratios (F5) was showing best release. F5 was compared with marketed and prepared conventional formulation and result shows better dissolution profile.
Co-Crystallization: A Novel Approach to Enhance the Dissolution of Poorly Soluble Drugs
2019
Approximately 40% of newly synthesized drugs are not able to enter market due to biopharmaceutical issues like poor solubility and poor permeability. Most number of drugs marketed is administered orally hence solubility enhancement plays a major role. There are different techniques to upgrade the dissolvability of inefficiently soluble drugs including pro-drug approach, salt formation, particle size reduction, complexation and solid dispersion. Out of all other techniques, salt formation is one of majorly used technique to improve physicochemical characteristics of drugs which includes formation of ionic bond. But nowadays development of co-crystals has evolved as a suitable technique towards improving the dissolvability and bioavailability of ineffectively soluble drugs that includes non-ionic bond formation. In this paper a brief and accurate precis of pharmaceutical co-crystals is stated with specific spotlight on co-crystal preparation methodologies, mechanism of co-crystal form...
New Trends in the Co-crystallization of Active Pharmaceutical Ingredients
Journal of Applied Pharmaceutical Science
Pharmaceutical materials science being a fundamental branch that continuously provides important insights, theories, and technologies to formulation sciences. The recent advances in this area have brought the possibility to produce pharmaceutical materials by design. In particular, the formation of co-crystals, i.e. crystalline molecular complexes of two-or more neutral molecules, represents a potential route to achieve pharmaceutical materials with improved properties of interest, including dissolution rate and stability under conditions of high relative humidity. Co-crystals consists of API and a stoichiometric amount of a pharmaceutically acceptable co-crystal former. Pharmaceutical co-crystals are nonionic supramolecular complexes and can be used to address physical property issues such as solubility, stability and bioavailability in pharmaceutical development without changing the chemical composition of the API. These can be constructed through several types of interaction, inc...
American Journal of PharmTech Research
Co-crystallization is an emerging approach for enhancing physicochemical properties like solubility, stability, bioavailability of poorly soluble drugs of BCS class II in pharmaceutical development without changing the chemical composition and considered better alternatives to optimize drug properties. Co-crystal is a crystalline entity consists of API and a stoichiometric amount of a pharmaceutically acceptable co-crystal former formed by intermolecular interactions like Hydrogen bonding, π-π stacking and Van der Waals forces. In this article, an overview of pharmaceutical cocrystals will be presented along with the intermolecular interactions (Chemistry of Co-crystals), methods of their preparations, characterization of co-crystals altered physicochemical properties. Furthermore, this article also gives a brief explanation about newer trends in co-crystals with application of co-crystals in medicines and industries.