Formulation and Evaluation of Controlled-Release Tablet of Zolpidem Tartrate by Melt Granulation Technique

The present investigation describes the influence of the concentration of PEG 6000 as a melt binder and ratio of HPMC K4M : PVP on Zolpidem tartrate controlled-release tablet formulations using 32 full factorial design. The ratio of HPMC K4M and PVP K30 (X1) and the concentration of melt binder (X2) were selected as independent variables, and drug release at 1 hr (Q1), 4 hr (Q4), 8 hr (Q8), diffusion coefficient (n), and release rate constant (K) were selected as a dependent variable. Tablets were prepared by melt granulation technique and evaluated for various evaluation parameters. It was observed that concentration of melt binder had significant effect on Q1, Q4, n, and K Binder concentration 25% w/w was found optimum. Optimized formulation (F7) showed good similarity with theoretical profile of drug. The X2 variable had a significant effect on dependent variables, and the X1 variable had no significant effect on dependent variables

Formulation and Evaluation of Transdermal Patch of Repaglinide

Repaglinide has the half life of 1 hour, and bioavailability in the body is 56% due to first-pass metabolism. The total daily dose of Repaglinide is 16 mg (e.g., 4 mg four times daily depending on meal patterns); hence, it required frequent dosing. Transdermal patch of Repaglinide was prepared to sustain the release and improve bioavailability of drug and patient compliance. Different formulations were prepared by varying the grades of HPMC and concentration of PVP K30 by solvent casting method. The prepared formulations were evaluated for various parameters like thickness, tensile strength, folding endurance, % elongation, % moisture content, % moisture uptake, % drug content, in vitro drug release, in vitro permeation, and drug excipient compatibility. A 32 full factorial design was applied to check the effect of varying the grades of HPMC (X1) and PVP concentration (X2) on the responses, that is, tensile strength, percentage drug released in 1 hr (Q1), 9 hr (Q9), and diffusion coefficient as a dependent variables. In vitro release data were fitted to various models to ascertain kinetic of drug release. Regression analysis and analysis of variance were performed for dependent variables. The results of the F2 statistics between factorial design batches and theoretical profile were used to select optimized batch. Batch F6 was considered optimum batch which contained HPMC K100 and PVP (1.5%), showed release 92.343% up to 12 hr, and was more similar to the theoretical predicted dissolution profile (f2 = 69.187)

FORMULATION AND EVALUATION OF MUCOADHESIVE BUCCAL TABLETS OF CARVEDILOL

Objective: The aim of the study was to formulate and evaluate mucoadhesive buccal tablets of carvedilol to avoid the first-pass metabolism. Methods: Mucoadhesive Buccal tablets of carvedilol were prepared by direct compression techniques using a combination of bioadhesive polymers such as hydroxypropyl cellulose (HPC) and polyethlyelne oxide WSR-1105 (PEO WSR-1105). In order to improve solubility of carvedilol, solid dispersion was prepared using poloxamer 188. A 32 Full factorial design was applied to investigate the combined effect of the two independent variables i.e. concentration of HPC (X1) and concentration of PEO WSR-1105(X2) on the dependent variables, % in vitro drug release at 1 h (Y1), % in vitro drug release at 4 h (Y2), mucoadhesive strength (Y3) and mucoadhesion time (Y4). Results: Optimized mucoadhesive buccal tablets shows in vitro drug release of 96.23±2.45 in 8 h, mucoadhesive strength of 18.20±1.44 g, mucoadhesion time 420±2.6 min and surface pH 6.75±0.015. Drug excipients compatibility study by FTIR showed no interaction between drug and excipients. Conclusion: From all parameters and experimental design evaluation, it was concluded that the drug release rate decreased with an increase the concentration of HPC and PEO WSR-1105 and mucoadhesion property increased with increase the concentration of PEO WSR-1105. The in vitro release kinetics revealed the Korsmeyer-Peppas model is followed and drug release is by anomalous diffusion

Termoreverzibilni mukoadhezivni in situ hidrogel za oftalmičku primjenu: dizajniranje i optimizacija koristeći kombinaciju polimera

The purpose of the study was to develop an optimized thermoreversible in situ gelling ophthalmic drug delivery system based on Pluronic F 127, containing moxifloxacin hydrochloride as a model drug. A 32 full factorial design was employed with two polymers Pluronic F 68 and Gelrite as independent variables used in combination with Pluronic F 127. Gelation temperature, gel strength, bioadhesion force, viscosity and in vitro drug release after 1 and 10 h were selected as dependent variables. Pluronic F 68 loading with Pluronic F 127 was found to have a significant effect on gelation temperature of the formulation and to be of importance for gel formation at temperatures 3336 ºC. Gelrite loading showed a positive effect on bioadhesion force and gel strength and was also found helpful in controling the release rate of the drug. The quadratic mathematical model developed is applicable to predicting formulations with desired gelation temperature, gel strength, bioadhesion force and drug release properties.Cilj rada bio je razvoj i optimizacija termoreverzibilnog sustava za isporuku lijekova koji gelira in situ. Sustav je napravljen na bazi Pluronic F 127, a sadrži moksifloksacin hidroklorid kao modelni lijek. U radu je primjenjeno 32 potpuno faktorijsko dizajniranje s dva polimera, Pluronic F 68 i Gelrite kao nezavisnim varijablama koji su kombinirani s Pluronic F 127. Kao zavisne varijable odabrane su temperatura geliranja, čvrstoća gela, jačina bioadhezije, viskoznost i in vitro oslobađanje lijeka nakon 1 i 10 h. Pronađeno je da Pluronic F 68 u kombinaciji s Pluronic F 127 ima značajan učinak na temperaturu geliranja u rasponu od 33 do 36 C. S druge strane, Gelrite ima povoljan učinak na jačinu bioadhezije, čvrstoću gela i oslobađanje lijeka. Razvijen je kvadratni matematički model pomoću kojeg se može predvidjeti temperatura geliranja, čvrstoća gela, jačina bioadhezije i oslobađanje ljekovite tvari

Plutajuće matriks tablete: Dizajniranje i optimizacija kombiniranjem polimera

The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing domperidone as a model drug. Box-Behnken design was employed in formulating the GFDDS with three polymers: hydroxypropyl methylcellulose K4M (HPMC K4M) (X1), Carbopol 934P (X2) and sodium alginate (X3), as independent variables. Floating lag time (FLT), total floating time (TFT), time required to release 50% of the drug (t50) and diffusion exponent (n) were selected as dependent variables. Seventeen formulations were prepared, dissolution data obtained was fitted to the power law and floating profiles were analyzed. HPMC loading was found to be significant for floating properties. Carbopol loading had a negative effect on floating properties but was found helpful in controlling the release rate of the drug. No significant effect of sodium alginate on floating properties was observed but it was important for gel formation. The quadratic mathematical model developed could be used to predict formulations with desired release and floating properties.Cilj rada bio je razvoj i optimizacija plutajućih sustava za isporuku lijekova u želucu (GFDDS) s domperidonom kao modelom lijeka. Box-Behnkenovo dizajniranje korišteno je u formuliranju GFDDS. Nezavisne varijable u dizajniranju bila su tri polimera: hidroksipropil metilceluloza K4M (HPMC K4M) (X1), Carbopol 934P (X2) i natrijev alginat (X3), a zavisne varijable usporeno vrijeme plutanja (FLT), ukupno vrijeme plutanja (TFT), vrijeme potrebno za oslobađanje 50% lijeka (t50) i difuzijski eksponent (n). Pripravljeno je ukupno sedamnaest formulacija. Analizirani su podaci o oslobađanju ljekovite tvari. Količina HPMC značajno utječe na svojstva plutanja, dok količina karbopola ima negativni učinak na svojstvo plutanja, ali kontrolira oslobađanje ljekovite tvari. Natrijev alginat nema značajni učinak na svojstva plutanja, ali utječe na stvaranje gela. Kvadratni matematički model može se upotrijebiti za predviđanje formulacija sa željenim profilom oslobađanja i svojstvima plutanja

Topoisomerase Inhibitors Addressing Fluoroquinolone Resistance in Gram-Negative Bacteria.

Since their discovery over 5 decades ago, quinolone antibiotics have found enormous success as broad spectrum agents that exert their activity through dual inhibition of bacterial DNA gyrase and topoisomerase IV. Increasing rates of resistance, driven largely by target-based mutations in the GyrA/ParC quinolone resistance determining region, have eroded the utility and threaten the future use of this vital class of antibiotics. Herein we describe the discovery and optimization of a series of 4-(aminomethyl)quinolin-2(1H)-ones, exemplified by 34, that inhibit bacterial DNA gyrase and topoisomerase IV and display potent activity against ciprofloxacin-resistant Gram-negative pathogens. X-ray crystallography reveals that 34 occupies the classical quinolone binding site in the topoisomerase IV-DNA cleavage complex but does not form significant contacts with residues in the quinolone resistance determining region

Formulation development and characterization of in-situ gel of Rizatriptan Benzoate for intranasal delivery

The present investigation was aimed to formulate and characterize ion-activated in-situ gel loaded with Rizatriptan Benzoate (RIZ) for intranasal administration for brain targeting. The gel was further optimized for process and formulation parameters by using 32 factorial design. The optimized batch having the concentrations of gellan gum and HPMC E15 LV 33.83 mg and 9.6 mg respectively. Gel strength and mucoadhesive strength of the optimized formulation were found to be 32.54 sec and 2580.50 dynes/cm2 respectively. Moreover, improved in-vitro and ex-vivo release profile of in-situ gel were observed in comparison to drug solution. In a nutshell, the developed formulation holds a great promise in overcoming the limitation associated with currently marketed RIZ formulations and illustrates the potential use of ion-activated in-situ gel to administer the drug by nasal route for brain targeting. Keywords: In-situ gel, Rizatriptan benzoate, Ion-activated, Gellan gum, HPMC E15 LV, Brain delivery, Migrain

Design of experiments and white analytical chemistry-driven green and sensitive spectrofluorimetric estimation of pregabalin in its pharmaceutical dosage forms and spiked human plasma

Abstract Background Pregabalin (PGB) is a medication with anticonvulsant, analgesic and anxiolytic properties, employed in the treatment of epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, opioid withdrawal syndrome and generalized anxiety disorder. Several spectrofluorimetric techniques have been documented for the determination of PGB in pharmaceutical dosage forms. However, these published methods typically involve the use of expensive and toxic organic solvents and reagents, as well as high reaction temperatures for PGB analysis. These components pose risks to aquatic life and the environment, making them less environmentally friendly and user-friendly. A recent advancement in analytical chemistry has introduced a white analytical approach, providing an economical, eco-friendly and user-friendly method for the development of analytical procedures. Objectives Therefore, a green and sensitive spectrofluorimetric determination of PGB, guided by white analytical chemistry principles, has been conducted utilizing distilled water as an environmentally friendly solvent. Methods The establishment of the spectrofluorimetric method involved employing the design of experiments approach to ensure a robust, precise and accurate estimation of PGB. Response surface analysis and optimization of critical procedural variables and responses were carried out using the central composite design. The validation of the developed method adhered to the guidelines outlined in ICH (International Council for Harmonization) Q2 (R1) and M10. Results The established spectrofluorimetric method was utilized to determine the PGB content in commercially available formulations and human plasma samples spiked with PGB. The obtained results were in accordance with the labeled claim of PGB in the formulations. The recovery of PGB in the spiked human plasma samples ranged from 85 to 90% of the spiked amount. Conclusions The greenness profiles of the published and suggested spectrofluorimetric methods for PGB estimation were evaluated and compared using the AGREE calculator, GAPI software and ESA tool. The suggested method demonstrated sensitivity, robustness, environmental friendliness and user-friendliness

Evaluation of skill-oriented training on enhanced syndromic case management (ESCM) of reproductive tract infections / sexually transmitted infections (RTI/STIs) of care providers from three-tier health-care system of Gujarat

Background: Enhanced syndromic case management (ESCM) deals with reproductive tract and sexually transmitted infections. Capacity building of service providers not only boosts the program but also inputs from them improve the quality of services. Objectives: To (1) identify problem areas from providers' perspectives and the gaps in knowledge and application and (2) assess the gains (if any) through pre and post-training evaluation. Materials and Methods: A total of 121 participants (medical/para medical) from various medical colleges, district/sub-district hospitals/ community health centers, and urban dispensaries across Gujarat were trained at a teaching institute. Trainings were of 2-3 days duration involving different learning methodology. Pre- and post-training evaluation were done on a designed pro forma and data were entered in MS office Excel 2007. Gains in knowledge/skills if any were assessed by comparing pre-/post-evaluation responses and applying test of significance (x2 test). Observations: Out of total 121 participants, half (60) were doctors and the rest were paramedics [staff nurse (SN) and lab technicians (LT)]. Doctors revealed significant gain in basics of reproductive tract infections (RTI) and sexually transmitted infections (STI), syndrome identification, STI/HIV co-infection, and ESCM and less gain in asymptomatic STI/ complications, vulnerability, male reproductive organs, causes of vaginal/urethral discharge, STI complications, cervical cancer screening, and limitation of syndromic management. Gain was statistically significant in basics of RTI/STI amongst adolescent in paramedics; lab technicians showed significant gain in knowledge of laboratory-related areas. Conclusion: Assessment revealed (1) poor baseline knowledge and (2) gains following training sometimes significant and other times not significant even in core areas. Quality monitoring and contents/ methodologies modification are essential for robust trainings. Gains in skills could not be assessed through this evaluation

Preparation and Characterization of Self-Microemulsifying Drug Delivery System of Olmesartan Medoxomil for Bioavailability Improvement

Olmesartan medoxomil (OLM) is an angiotensin II receptor blocker (ARB) antihypertensive agent administered orally that has absolute bioavailability of only 26% due to the poor aqueous solubility (7.75 μg/ml). The aim of the present investigation was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral absorption of OLM. The solubility of OLM in various oils, surfactants, and cosurfactants was determined. Pseudoternary phase diagrams were constructed using Acrysol EL 135, Tween 80, Transcutol P, and distilled water to identify the efficient self-microemulsification region. Prepared SMEDDS was further evaluated for its emulsification time, drug content, optical clarity, droplet size, zeta potential, in vitro dissolution, and in vitro and ex vivo drug diffusion study. The optimized formulation S2 contained OLM (20 mg), Tween 80 (33%v/v), Transcutol P (33%v/v), and Acrysol EL 135 (34%v/v) had shown the smallest particle size, maximum solubility, less emulsification time, good optical clarity, and in vitro release. The in vitro and ex vivo diffusion rate of the drug from the SMEDDS was significantly higher than that of the plain drug suspension. It was concluded that SMEDDS would be a promising drug delivery system for poorly water-soluble drugs by the oral route