Dexibuprofen enteric film-coated tablets: design, characterization and pharmacokinetic analysis in human volunteers.

OBJECTIVE: This study aimed to develop a stable and scalable enteric film-coated tablet for the gastric irritant dexibuprofen. METHODS: Utilizing direct compression with super-disintegration (crospovidone), the optimal core batches were coated with Opadry white seal coat and enterically coated with Eudragit®L100 with pigment (Talc), demonstrating a 12% weight increase; release and integrity were assessed using specific pH buffers and SEM, with stability testing confirming a six-month shelf life at 40 °C and 75% RH. RESULTS: The optimized formulation achieved 99.87% release in phosphate buffer within 60 min, maintained integrity for 120 min in acidic conditions, and exhibited superior bioavailability compared to Innovifen with relative bioavailability ≈of 121% and elevated Cmax (18.35 µg/ml compared to 11.1 µg/ml). CONCLUSION: These results highlight the potential of this formulation to enhance patient safety and efficacy through delayed enteric technology and fast intestinal release.

Empagliflozin: HPLC based analytical method development and application to pharmaceutical raw material and dosage form.

The current investigation is based on efficient method development for the quantification of empagliflozin in raw and pharmaceutical dosage forms, as no pharmacopoeial method for the drug is available so far. The developed analytical method was validated as per ICH guidelines. C18 column with mobile phase (pH 4.8) consisted of 0.1% trifluoroacetic acid solution and acetonitrile (70:30 v/v) was used for drug analysis. The calibration plot showed good linear regression (r2>0.999) over the concentration of 0.025-30 µg mL-1. The LOD and LOQ were found to be 0.020 µg mL-1 and 0.061 µg mL-1, respectively. The percentage recovery was estimated between 98.0 to 100.13%. Accuracy and precision data were found to be less than 2%, indicating the suitability of method for routine analysis in pharmaceutical industries. Moreover, the drug solution was found to be stable in refrigerator and ambient room temperature with mean % accuracy of >98%. Empagliflozin contents were also tested in both the raw API and marketed tablet brands using this newly developed method. The mean assay of raw empagliflozin and tablet brands were ranged from 99.29%±1.12 to 100.95%±1.69 and 97.18%±1.59 to 98.92%±1.00 respectively. Based on these findings, the present investigated approach is suitable for quantification of empagliflozin in raw and pharmaceutical dosage forms.

Optimization of empagliflozin immediate release tablets (10 mg) using central composite rotatable design with response surface methodology.

Empagliflozin is a selective inhibitor of sodium glucose co-transporter II, given as mono therapy or an add-on treatment to reduce the glycated hemoglobin levels in type 2 diabetes. This work deals with designing, formulating and optimizing empagliflozin (10mg) immediate release (IR) tablets by direct compression technique using different excipients. Through central composite rotatable design (CCRD), total nine formulations (EF1-EF9) were generated by changing the composition of binder avicel PH 102® (X1) and superdisintegrant acdisol⌖ (X2). Formulation runs with in suitable weight range and powder properties were subjected to compression. The influence of interaction of excipients on friability (Y1), hardness (Y2) and disintegration (Y3) were analyzed by fitting the polynomial quadratic model with response surface methodology (RSM). Trials EF2, EF7, EF8 and EF9 exhibited acceptable tablet attributes upon physico-chemical testing. Different dissolution models were applied to observe the in vitro drug release pattern in phosphate buffer of pH 6.8. The cumulative drug release of IR tablet batches followed the Weibull kinetics with regression coefficient (r2) values of 0.983-0.992. Empagliflozin trials were exposed to accelerated storage conditions (40±2°C/ 75±5% RH) for stability testing. Shelf life period of exposed formulations were computed in range of 22 to 25 months. Keeping in view of the results, it is concluded that the employed technique of preparation and optimization are observed to be excellent for developing immediate release empagliflozin (10mg) tablets.

Dexibuprofen: Statistical assessment of drug release kinetics and investigative quality perspective.

Healthcare professionals including physicians and pharmacists have been trying since long to come across and work out regarding the issue of generic alternatives, which is highly affected by factors like therapeutic efficacy, cost effectiveness, aesthetic and elegant appearance and implementation of packaging number over the drug product. However, the community pharmacist professionals are also facing difficulty in making decision regarding selection and dispensing the most efficacious brand to the patients. In this regard, the initiation of recent approaches for the development of amenable drug products has led to evolve the concept of generating new avenues for achieving higher patient compliance. Hence, the objective of this study was to evaluate the quality attributes and make comparisons regarding different brands of Dexibuprofen available in market of Karachi, Pakistan. The study is based on evaluation of physical chemical parameters of five different brands. Moreover, a comparative dissolution profile of selected brands of Dexibuprofen was also performed by applying numerous approaches. DEX-1was selected as reference while DEX-2- DEX-5 was selected as test brands. Results of all the selected brands met all the compendial requirements. Interpretation of the entire aforementioned test was evaluated using model independent, model- dependent and one - way ANOVA. The work presented in this study has been designed to provide quality standard products easily accessible in Pakistani market.

Formulation design, characterization and optimization of cinitapride (1mg) immediate release tablets using direct compression technology.

Cinitapride hydrogen tartarate is relatively a new prokinetic agent that widely prescribed for GERD and epigastric pain. Present study was aimed to develop and optimize cinitapride (1 mg) immediate release (IR) tablet formulation(s) by direct compression using central composite rotatable technique. Overall nine formulations (FC1-FC9) were generated by varying the composition of binder avicel PH 102 (X1) and superdisintegrant crospovidone (X2). The effect of interaction of excipients on hardness (Y1), friability (Y2), disintegration (Y3) and dissolution at 15 min (Y4) were analyzed by RSM plotting. On the basis of physico-chemical evaluation FC3, FC4 and FC6 were found to be the optimized formulations however; FC3 was selected to be the best trial owing to excellent drug release (100.17%) with least friability (0.14%). These IR tablets showed the release pattern similar to the Weibull model with r2 value of 0.978-0.998. The dissimilarity (f1) and similarity indexes (f2) of FC3, FC4, FC6 with the marketed product were estimated to be 2.57 and 76.51, 4.51 and 64.46, 4.32 and 66.78 respectively. Trial optimized formulations were highly stable with the shelf lives of 58-64 months. So, keeping in view the results of present investigation, it is concluded that the technique of manufacturing and optimization is found to be excellent for developing immediate release cinitapride tablets.

Adult Pgf-/- mice behaviour and neuroanatomy are altered by neonatal treatment with recombinant placental growth factor.

Offspring of preeclamptic pregnancies have cognitive alterations. Placental growth factor (PGF), is low in preeclampsia; reduced levels may affect brain development. PGF-null mice differ from normal congenic controls in cerebrovasculature, neuroanatomy and behavior. Using brain imaging and behavioral testing, we asked whether developmentally asynchronous (i.e. neonatal) PGF supplementation alters the vascular, neuroanatomic and/or behavioral status of Pgf-/- mice at adulthood. C57BL/6-Pgf-/- pups were treated intraperitoneally on postnatal days 1-10 with vehicle or PGF at 10 pg/g, 70 pg/g or 700 pg/g. These mice underwent behavioral testing and perfusion for MRI and analysis of retinal vasculature. A second cohort of vehicle- or PGF-treated mice was perfused for micro-CT imaging. 10 pg/g PGF-treated mice exhibited less locomotor activity and greater anxiety-like behavior relative to vehicle-treated mice. Depressive-like behavior showed a sex-specific, dose-dependent decrease and was lowest in 700 pg/g PGF-treated females relative to vehicle-treated females. Spatial learning did not differ. MRI revealed smaller volume of three structures in the 10 pg/g group, larger volume of seven structures in the 70 pg/g group and smaller volume of one structure in the 700 pg/g group. No cerebral or retinal vascular differences were detected. Overall, neonatal PGF replacement altered behavior and neuroanatomy of adult Pgf-/- mice.