A new design for a chronological release profile of etodolac from coated bilayer tablets: In-vitro and in-vivo assessment

Repeated dose medication usually maximizes adverse effects, while sustained release systems did not offer a fast onset of action. Etodolac was formulated to enable pulsatile and sustained drug release, which was chronologically more suitable as an anti-inflammatory drug. Eudragit® RSPO, Eudragit® RLPO, and HPMC K15M were added in the sustained release layer and tried in different ratios. Croscarmellose sodium or sodium starch glycolate were used as superdisintegrants for the fast release layer offering the loading dose for rapid onset of drug action. Bilayer tablets were successively coated with Opadry®II, HPMC K4M and E5 (1:40), and Surelease®. All formulations complied with the Pharmacopeial standards for post-compression parameters. In-vitro release profile illustrated a lag-time of 4 h followed by a rapid loading dose release for 2 h. A prolonged steady state release with a t1/2 of 11 h lastly occurred. The coated bilayer tablet showed pulsatile and sustained release effects in rats. The licking time and swelling degree were tested and results demonstrated significant difference (P < 0.05) between the sustained anti-inflammatory action of formulation C1 compared to other groups. Therefore the new chronological design could provide a consistent drug release over 24 h with good protection against associated symptoms of gastric release. Keywords: Pulsatile release, Sustained release, Etodolac, Bilayer tablet, Opadry, Sureleas

Development and validation of sensitive and rapid UPLC–MS/MS method for quantitative determination of daclatasvir in human plasma: Application to a bioequivalence study

A rapid and sensitive UPLC–MS/MS method was developed and validated for determination of daclatasvir (DAC) in human plasma using sofosbuvir (SOF) as an internal standard (IS). The Xevo TQD LC–MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Precipitation with acetonitrile was used in sample preparation. The prepared samples were chromatographed on Acquity UPLC HSS C18 (50 × 2.1 mm, 1.8 μm) column by pumping 10 mM ammonium formate (pH 3.5) and acetonitrile in an isocratic mode at a flow rate of 0.30 ml/min. Method validation was performed as per the FDA guidelines and the standard curves were found to be linear in the range of 5–4000 ng/ml for DAC. The intra-day and inter-day precision and accuracy results were within the acceptable limits. A very short run time of 1.2 min made it possible to analyze more than 500 human plasma samples per day. The wider range of quantification of DAC allowed the applicability of the developed method for its determination in a bioequivalence study in human volunteers

Quantification of sofosbuvir and ledipasvir in human plasma by UPLC–MS/MS method: Application to fasting and fed bioequivalence studies

A rapid and sensitive LC–MS/MS method was developed, optimized and validated for quantification of sofosbuvir (SF) and ledipasvir (LD) in human plasma using eplerenone as an internal standard (IS). Analytes and IS were extracted from plasma by simple liquid–liquid extraction technique using methyl tertiary butyl ether. The prepared samples were chromatographed on Acquity UPLC BEH C18 column. Separation was done using a mobile phase formed of 0.1% formic acid and acetonitrile (50:50, v/v) in an isocratic mode at a flow rate of 0.4 ml/min. The Xevo TQD LC–MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. A full validation of the method was performed according to the FDA guidelines. Linearity was found to be in the range of 0.25–3500 ng/ml for SF and 5–2000 ng/ml for LD. The intra-day and inter-day precision and accuracy results were within the acceptable limits. A short run time of 2 min allows analysis of more than 400 plasma samples per day. The developed method was successfully applied to both fasting and fed bioequivalence studies in healthy human volunteers

Comparative Pharmaceutical Study on Colon Targeted Micro-particles of Celecoxib: In-vitro- Invivo Evaluation

In order to target celecoxib which is a COX2 inhibitor, with potentials in the prevention and treatment of colitis and colon cancer, it was formulated as microparticles using solvent /evaporation method and various pH dependent Eudragit polymers .The in-vitro evaluation of the prepared microparticles showed spherical and smooth morphology. The encapsulation efficiency and yield were high indicating that the method used is simple and efficient at this scale. The in-vitro release study showed no release in acidic medium for 2 hr followed by the release of the drug in pH 6.8 in case of Eudragit L100-55 and L100 and pH 7.4 in case of Eudragit S100. The pharmacokinetic parameters were calculated and method validation was performed to insure that it is suitable and reliable. . Pharmacokinetic parameters were investigated by determining the Cmax, T max , AUC0-t, Kel , and T1/2 of the drug as a suspension and as microparticles .There was a significant difference (P<0.05) in Tmax between the drug as a suspension and as microparticles. The effect of celecoxib on the degree of inflammation was examined on acetic acid induced colitis rat model and the drug was given as a suspension and as microparticles . The evaluation was done using macroscopical,microscopical and biochemical examination. There was a significant difference between the acetic acid control group and the treatment groups regarding all examination criteria in the order microparticles formulated using Eudragit S100 followed by Eudragit L100-55 while microparticles using Eudragit L100 and drug suspension showed almost the same results

Fluconazole-loaded solid lipid nanoparticles topical gel for treatment of pityriasis versicolor: formulation and clinical study

Solid lipid nanoparticles (SLNs) are very potential formulations for topical delivery of antifungal drugs. Hence, the purpose of this research was to formulate the well-known antifungal agent Fluconazole (FLZ)-loaded SLNs topical gel to improve its efficiency for treatment of Pityriasis Versicolor (PV). FLZ-SLNs were prepared by modified high shear homogenization and ultrasonication method using different concentration of solid lipid (Compritol 888 ATO, Precirol ATO5) and surfactant (Cremophor RH40, Poloxamer 407). The physicochemical properties and the in vitro release study for all FLZ-SLNs were investigated. Furthermore, the optimized FLZ-SLN formula was incorporated into gel using Carpobol 934. A randomized controlled clinical trial (RCT) of potential batches was carried out on 30 well diagnosed PV patients comparing to market product Candistan® 1% cream. Follow up was done for 4 weeks by clinical and KOH examinations. The results showed that FlZ-SLNs were almost spherical shape having colloidal sizes with no aggregation. The drug entrapment efficiency ranged from 55.49% to 83.04%. The zeta potential values lie between −21 and −33 mV presenting good stability. FLZ showed prolonged in vitro release from SLNs dispersion and its Carbapol gel following Higuchi order equation. Clinical studies registered significant improvement (p < .05) in therapeutic response (1.4-fold; healing%, 4-fold; complete eradication) in terms of clinical cure and mycological cure rate from PV against marketed cream. Findings of the study suggest that the developed FLZ loaded SLNs topical gels have superior significant fast therapeutic index in treatment of PV over commercially available Candistan® cream

Effect of Formulation Parameters on the Preparation of Superporous Hydrogel Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Carvedilol

The purpose of this study was to formulate a superporous hydrogel (SPH) containing carvedilol self-nanoemulsifying drug delivery system. Effects of formulation parameters (amount of SPH and 0.1 N HCl used during drug loading) were studied in 32 factorial design. Response surface plots showed significant effect of the parameters on hydrogel swelling, carvedilol content, and carvedilol in vitro release. Regression equations were generated to calculate the desirable responses