FORMULATION AND EVALUATION OF NEUSILIN US2 ADSORBED AMORPHOUS SOLID SELF-MICROEMULSIFYING DELIVERY SYSTEM OF ATORVASTATIN CALCIUM ®

ABSTRACTObjective: The objective of the present study was to improve the dissolution profile of poorly water-soluble atorvastatin calcium (ASC), via formationof its solid self-microemulsifying drug delivery system (SSMEDDS).Methods: The SSMEDDS was prepared using oleic acid, Tween 80 and propylene glycol as an oil phase, surfactant, and co-surfactant, respectively.Initially, the solubility of ASC was examined in different oils, surfactants and co-surfactants, and pseudo-ternary phase diagrams were constructedsubsequently to optimize the ratio of the excipients having greater microemulsion region. The liquid self-emulsifying batches of ASC were developedwith the optimized excipients and evaluated for droplet size, zeta potential, percentage transmittance, self-emulsification time assessment, dispersibilitytest, and drug release. Neusilin US2 was employed as an adsorbent to transform optimized liquid emulsifying batch A1 to solid formulation. The solidformulation was characterized by particle size analysis, differential scanning calorimetry, X-ray powder diffractometry, scanning electron microscopy,and in vitro drug release.®Results: The characterization studies revealed the transformation of crystalline ASC to amorphous form in solid adsorbed batch. The drug releasestudies demonstrated remarkable improvement in dissolution profile of ASC from its liquid as well as SSMEDDS as compared to pure drug.Conclusion: The development of SSMEDDS could be a reliable and alternative approach for improvement of dissolution performance of ASC.Keywords: Atorvastatin, Self-microemulsifying, Amorphous, Formulation, Neusilin® US2

PREPARATION, CHARACTERIZATION, AND EVALUATION OF ANTI-INFLAMMATORY ACTIVITY OF ETORICOXIB LOADED SOLUPLUS® NANOCOMPOSITES

Objective: The objective of this study was to prepare and characterize etoricoxib (ECB) loaded Soluplus® nanocomposites to improve its physicochemical properties. The effect of polymer and surfactant concentration on particle size, in vitro percentage dissolution efficiency and the anti-inflammatory activity of nanocomposites were also investigated.Methods: The nanocomposites were prepared by using a freeze-drying technique. The analytical evidence for the formulation of lyophilized nanocomposites in solid state were generated and confirmed by differential scanning calorimetry (DSC), fourier transformation infrared spectroscopy (FTIR), x-ray powder diffractometry (XPRD) and scanning electron microscopy (SEM). The in vitro drug release profile of nanocomposites was compared with pure ECB powder.Results: The nanocomposites of ECB were contained in a nano range with particle size and zeta potential of 63.5 nm and 46.5 mv, respectively. The solubility and dissolution of the nanocomposites were significantly (p<0.001) improved as compared to ECB alone, evidenced by decreased log P values (1.90±0.002) of the nanocomposites. The characterization studies revealed the formation of amorphous nanocomposites of ECB with existence of physical interactions between drug and polymer. The anti-inflammatory activity of nanocomposites evaluated by carrageenan-induced rat paw edema model demonstrated nonsignificant (p>0.05) increase in anti-inflammatory activity as compared to pure ECB.Conclusion: From the results, it could be concluded that the formation of ECB nanocomposites with Soluplus® could be an effective and alternative approach to modify the physicochemical properties of ECB

Studies on in-vitro transcutaneous delivery of losartan potassium, influence of penetration enhancers and barrier membrane

Formulation and in vitro evaluation of losartan potassium (LP) loaded transdermal delivery system (TDS) was investigated for controlled release and improved therapeutic efficacy. TDS (patches) were prepared by varying the composition of Eudragit RL 100 and Eudragit RS 100 (5:0, 4:1, 3:2, 2.5:2.5, 2:3, 1:4 and 0:5). Patches were evaluated for thickness, content uniformity, mechanical properties, moisture uptake and in vitro drug release. Technological parameters for all the formulations were found to be within the limit. In vitro studies showed relatively high permeation of LP (F1- 42.17 ± 1.13 %) from the formulation comprising 4:1 ratio of polymer. Inclusion of capsaicin (55.70 ± 1.55 %) and pluronic F-68 (70.88 ± 1.20 %) to formulation F1 resulted increased permeation of LP across human skin. In conclusion, this study demonstrated the potential of simple transdermal adhesive patch incorporating LP to deliver therapeutically useful dose in-vivo for the treatment of hypertension.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Development and characterization of ternary solid dispersion systems of olmesartan medoxomil

The ternary solid dispersion systems of poorly water soluble olmesartan medoxomil (OLM) were prepared by conventional kneading method in order to improve its physicochemical performance. A 32 full factorial design approach was employed to optimize influence of concentration of polyvinylpyrrolidone K30 (PVP) and poloxamer 407 (PLX) on physicochemical characteristics of these dispersions. All formulations were characterized by XRPD, DSC and dissolution studies. Physical studies revealed complete loss of crystallinity and formation of uniform molecular dispersion of OLM in its ternary systems. All dispersion systems showed significant improvement in dissolution profile in comparison to pure drug alone (p 2 : 68.43 ± 2.8 %) of OLM suggesting optimum ratio of carrier system. The kinetic study of dissolution displayed to follow the Korsmeyer-Peppas model (r2 = 0.9835).Colegio de Farmacéuticos de la Provincia de Buenos Aire

Physicochemical characterization and improved in vitro dissolution performance of diacerein solid dispersions with PVP K30

Solid dispersions (SDs) of poorly water soluble diacerein were prepared with polyvinylpyrrolidone K30 at drug to polymer ratios of 1:1, 1:3 and 1:5 w/w utilizing kneading technique. Physical mixture (PM) was prepared at drug to polymer ratio of 1:5 w/w for comparison. All formulations were further characterized by TLC, DSC, XRPD, SEM and dissolution studies. TLC indicated an absence of chemical interaction between drug and polymer. A prominent decrease in the crystallinity was accounted for diacerein in binary systems from XRPD data. DSC thermograms revealed a uniform molecular dispersion and generation of amorphous entities of drug accompanied by loss of crystalline and irregular shape with distinct changes in surface morphological features of diacerein detected in SEM photomicrographs. The drug dissolution properties of SDs were significantly improved (DP2: 95.87-100%) in comparison to crystalline diacerein and PM suggesting suitability of kneading method for improving the release rate properties of diacerein.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Physicochemical characterization and improved in vitro dissolution performance of diacerein solid dispersions with PVP K30

Solid dispersions (SDs) of poorly water soluble diacerein were prepared with polyvinylpyrrolidone K30 at drug to polymer ratios of 1:1, 1:3 and 1:5 w/w utilizing kneading technique. Physical mixture (PM) was prepared at drug to polymer ratio of 1:5 w/w for comparison. All formulations were further characterized by TLC, DSC, XRPD, SEM and dissolution studies. TLC indicated an absence of chemical interaction between drug and polymer. A prominent decrease in the crystallinity was accounted for diacerein in binary systems from XRPD data. DSC thermograms revealed a uniform molecular dispersion and generation of amorphous entities of drug accompanied by loss of crystalline and irregular shape with distinct changes in surface morphological features of diacerein detected in SEM photomicrographs. The drug dissolution properties of SDs were significantly improved (DP2: 95.87-100%) in comparison to crystalline diacerein and PM suggesting suitability of kneading method for improving the release rate properties of diacerein.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Physicochemical characterization and improved in vitro dissolution performance of diacerein solid dispersions with PVP K30

Solid dispersions (SDs) of poorly water soluble diacerein were prepared with polyvinylpyrrolidone K30 at drug to polymer ratios of 1:1, 1:3 and 1:5 w/w utilizing kneading technique. Physical mixture (PM) was prepared at drug to polymer ratio of 1:5 w/w for comparison. All formulations were further characterized by TLC, DSC, XRPD, SEM and dissolution studies. TLC indicated an absence of chemical interaction between drug and polymer. A prominent decrease in the crystallinity was accounted for diacerein in binary systems from XRPD data. DSC thermograms revealed a uniform molecular dispersion and generation of amorphous entities of drug accompanied by loss of crystalline and irregular shape with distinct changes in surface morphological features of diacerein detected in SEM photomicrographs. The drug dissolution properties of SDs were significantly improved (DP2: 95.87-100%) in comparison to crystalline diacerein and PM suggesting suitability of kneading method for improving the release rate properties of diacerein.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Fizikokemijska karakterizacija čvrstih disperzijskih sustava tadalafila s poloksamerom 407

Dissolution behaviour of a poorly water-soluble drug, tadalafil, from its solid dispersion systems with poloxamer 407 has been investigated. Solid dispersion systems of tadalafil were prepared with poloxamer 407 in 1:0.5, 1:1.5 and 1:2.5 ratios using the melting method. Characterization of binary systems with FTIR and powder XRPD studies demonstrated the presence of strong hydrogen bonding interactions, a significant decrease in crystallinity and the possibility of existence of amorphous entities of the drug. In the binary systems tested, 1:0.5 proportion of tadalafil/poloxamer 407 showed rapid dissolution of tadalafil (DE30 70.9 ± 3.6 %). In contrast, higher proportions of poloxamer 407 (1:1.5 and 1:2.5) offered no advantage towards dissolution enhancement of the drug from corresponding binary systems indicating altered rheological characteristics of the polymer, at its higher concentration, which might have retarded the release rate of tadalafil.U radu je ispitivano oslobađanje u vodi teško topljivog lijeka tadalafila iz čvrstih disperzijskih sustava. Ti sustavi pripravljeni su s poloksamerom 407 u omjeru lijeka i polimera 1:0,5, 1:1,5 i 1:2,5, koristeći metodu taljenja. Karakterizacija binarnih sustava s FTIR i rendgenskom difrakcijom praha XRD ukazuje na prisutnost snažnih vodikovih veza, značajno smanjenje kristaliničnosti i moguću prisutnost amorfnog lijeka. Iz binarnog sustava tadalafil/poloksamer 1:0,5 oslobađanje ljekovite tvari je brzo (DE30 70,9 ± 3,6 %). Nasuprot tome, iz pripravaka s višim omjerima lijeka i polimera (1:1,5 i 1:2,5) oslobađanje ljekovite tvari nije povećano. Usporavanje oslobađanja tadalafila moglo bi biti posljedicom promjene reoloških svojstava polimera pri višim koncentracijama

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Inclusion complexes of cefuroxime axetil with β-cyclodextrin: Physicochemical characterization, molecular modeling and effect of l-arginine on complexation

AbstractThe inclusion complexes of poorly water-soluble cephalosporin, cefuroxime axetil (CFA), were prepared with β-cyclodextrin (βCD) with or without addition of l-arginine (ARG) to improve its physicochemical properties. We also investigated the effect of ARG on complexation efficiency (CE) of βCD towards CFA in an aqueous medium through phase solubility behaviour according to Higuchi and Connors. Although phase solubility studies showed AL (linear) type of solubility curve in presence and absence of ARG, the CE and association constant (Ks) of βCD towards CFA were significantly promoted in presence of ARG, justifying its use as a ternary component. The solid systems of CFA with βCD were obtained by spray drying technique with or without incorporation of ARG and characterized by differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM), and saturation solubility and dissolution studies. The molecular modeling studies provided a better insight into geometry and inclusion mode of CFA inside βCD cavity. The solubility and dissolution rate of CFA were significantly improved upon complexation with βCD as compared to CFA alone. However, ternary system incorporated with ARG performed better than binary system in physicochemical evaluation. In conclusion, ARG could be exploited as a ternary component to improve the physicochemical properties of CFA via βCD complexation