Compatibility Studies Research Articles

An Aza-michael Addition Product Causes Incompatibility Between Etacrynic Acid and Theophylline in a Paediatric Cardiological ICU.

In a compatibility study of parenteral drugs commonly used in paediatric cardiological intensive care units, an unknown reaction product was found in a mixture of etacrynic acid and theophylline. The conditions in terms of the concentration of etacrynic acid and theophylline as well as the materials used corresponded to the conditions in the intensive care unit. Initially, the reaction product appeared as a significant and increasing peak in the chromatograms when determining the content of etacrynic acid and theophylline via HPLC. At the same time, the concentrations of both drugs decreased. A literature search in the chemical databases Reaxys® and Scifinder ® revealed a patent from 1967 describing an aza-Michael addition between etacrynic acid and theophylline to either N-7 or N-9. Using LC-MS/MS experiments, we were able to confirm that Michael-like reaction between etacrynic acid and theophylline occurs. To elucidate the exact structure of the reaction product we performed NMR experiments (COSY, HSQC and HMBC). With the acquired data we were finally able to identify the unknown compound as the N-7 substituted adduct [2-(2,3-dichloro-4-{2-[(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)methyl]butanoyl}phenoxy)acetic acid]. Our findings show that etacrynic acid and theophylline should not be mixed and should be administered through separate venous lines when infused.

Enhancing Oral Absorption of Orlistat through Gastroretentive Mucoadhesive Pellets: Formulation and Evaluation

Aim: The aim of this study was to develop gastroretentive mucoadhesive pellets of Orlistat to improve its oral bioavailability and enhance its absorption.
 Methods: Orlistat pellets were prepared using Hydroxy Propyl Methyl Cellulose (HPMC) K100M, Sodium Carboxy Methyl Cellulose (NaCMC), Carbopol 934P, and Polyvinyl Pyrrollidone (PVP) K30 in varying ratios. Physical characteristics of the tablets were evaluated, and compatibility studies were performed between Orlistat and the excipients. Swelling index, mucoadhesion strength and drug release were measured for each formulation. Drug release kinetics and stability studies were carried out.
 Results: The combination of HPMC K100M, NaCMC, Carbopol 934P and PVP K30 provided balanced release and mucoadhesion with F13 showing sustained release up to 16 hours. The calibration curve demonstrated a good linear relationship between Orlistat concentration and absorbance over the range of 10 to 50 ?g/ml. Swelling index increased with time and polymer concentration and mucoadhesion strength increased with polymer viscosity and concentration. Drug release from formulations containing HPMC K100M, NaCMC and Carbopol 934P were 12-14 hours, 10-12 hours and 8-11 hours, respectively. Combination polymers in F10-F13 provided balanced release and mucoadhesion, with F13 showing sustained release up to 16 hours. The drug release followed zero order kinetics with non-Fickian diffusion. Stability studies on the optimized F13 formulation showed no significant changes in appearance, hardness, mucoadhesion or drug release over 3 months.
 Conclusion: The combination of HPMC K100M, NaCMC, Carbopol 934P and PVP K30 improved the oral bioavailability and absorption of Orlistat. The study demonstrated the importance of compatibility studies and the use of calibration curves for quantitative analysis. The findings provide valuable insights into the development of drug delivery systems for poorly bioavailable drugs.

Formulation and characterization of polyherbal anti-acne gel containing Citrus aurantifolia and Aloe barbadensis extracts for the management of acne vulgaris

The antibiotic used to treat acne may develop antibiotic resistance and side effects. Meanwhile, treating acne-causing bacteria by applying Citrus aurantifolia juice to the skin immediately is ineffective. Citrus aurantifolia juice was employed in an anti-acne gel formulation to treat acne that was caused by Cutibacterium acnes and Staphylococcus epidermidis has no synergistic therapeutic effect shown. Additionally, polyherbal formulations are currently in high demand in the global market. The herbal industry's global market value has risen dramatically from US$60 billion in 2000 to US$105 billion in 2017. The worldwide market will increase at a rate of 7.6% each year until it reaches $5 trillion in 2050. This study aims to formulate a polyherbal anti-acne gel containing C. aurantifolia and Aloe barbadensis, and to characterize the formulated gel for its physicochemical properties. The phytoconstituents found in plant extracts were also analysed. The antibacterial activity of plant extracts against Staphylococcus aureus was also investigated using an agar well diffusion method. After plant extracts were discovered, gels with varying concentrations of plant extracts, and excipients were prepared along with compatibility studies. Parameters like colour, odour, homogeneity, phase separation, consistency, washability, pH, viscosity, spreadability and antibacterial activity were evaluated. The results showed that the levels of phenol, tannins, and flavonoids in plant extracts varied, the antibacterial activity of plant extracts was studied with a clear inhibition zone demonstrated, and plant extracts were compatible with all excipients. Gel formulations containing C. aurantifolia, A. barbadensis, the excipients Carbopol-940, methylparaben, propyl paraben, propylene glycol-400, triethanolamine and water have been developed. The formulated gels were clear, odourless, uniform, consistent, without lumps, and washable. It was found that pH was closer to the skin, good viscosity and spreadability. The formulated gel, F4 has greater antibacterial activity than plant extracts and other formulations with a larger diameter inhibition zone. It is concluded that the polyherbal anti-acne gel containing C. auranfolia and A. barbadensis can be formulated which has a high potential for halal cosmetics product development. However, more research should be done before it can be commercialised by comparing it to commercially available marketed formulations to treat acne vulgaris.

Awareness of Physicians on Celiac Disease and the Effect of Education

Celiac disease is a genetic in origin, systemic autoimmune disease that can be occur at any stage of life. The onset of the disease is triggered by dietary intake of wheat, barley and rye containing gluten prolamins. The prevalence of the disease is around 1% and this rate is expected to increase as awareness increases. Due to celiac disease mimicking the symptoms of other diseases and being known as a rare disease, the diagnosis rate is low, and patients are often diagnosed late. In this study, we evaluated the awareness rates of physicians and investigated the effect of celiac training on awareness rate. Our research is a pre-test and post-test compatibility study prepared in cross-sectional style. Family physicians who participated in the meeting on May 9, 2019, Celiac Day were included in our study. The pre-test was distributed to physicians just before the meeting. A training module on celiac disease was presented to the participants and a final test was performed afterwards. When the pre-test and post-test were matched, the questionnaires of 88 physicians were analyzed. Kappa coefficient was calculated for nominal scale information and Kendall’s tau-b correlation coefficient for ordinal scale questions were calculated. A binary logistic regression model was created according to the situation of encountering celiac patients in the study environment. In the whole study, type-I error value was taken as 5% and p<0.05 value was accepted as statistically significant. The mean age of the participants was 30.91±6.69 years. The mean number of patients suspected of celiac disease was 3.13 in the participants who stated that they had seen 767 patients in a month. The mean for patients diagnosed with celiac disease was 1.56 in the last year. When celiac-related conditions are evaluated, the states with the highest awareness are chronic diarrhea (100%), weight loss (98.9%), and anemia (96.6%), respectively, while the least common conditions were genetic syndromes (14.8-20.5%) and gynecological problems and infertility (39.8-42%). In the last test after the training, it was found that almost all the awareness was around 90%. The change between pre-test and post-test was significant for most statements (p<0.001). When the comparisons between the pre-test and post-test on the self-sufficient visual scale provided to the physicians were made, the difference was observed as significant in both (Wilcoxon test, p <0.001). Chronic diarrhea, weight loss, anemia, and dyspepsia were the most well-known conditions related to celiac disease in our study, while gynecological problems and genetic syndromes were the least known. It was determined that typical celiac disease is known more, and atypical celiac disease is less known. At the end of the training, it was observed that the awareness rate increased in all findings. The results of the study support that reminding of celiac disease with in-service training given both in residency training and in primary care can increase the diagnosis rates.

ANALYSIS OF THE CONTROL SYSTEM OF A WIND PLANT CONNECTED TO THE AC NETWORK

The dynamics of the development of alternative power sources over the past few decades are presented, which gives reason to talk about the trends in the further development of wind energy. An analysis of the structures and technical characteristics of wind generators is provided, namely, types of electric motors, power circuits of semiconductor converters that provide the generation of electrical energy to the general industrial electrical network. The issue of the possibility of operation of wind generators in wide wind ranges, the issue of emission of reactive power and higher harmonics of currents to the general industrial electrical network, as well as the issue of the efficiency of various structures of wind generators are considered. A wind turbine control system with an asynchronous generator is proposed. A study of transient control processes and energy compatibility of a full energy conversion wind turbine with a power supply network by simulation computer modeling in the Matlab / Simulink software environment is given. The obtained result indicates the possibility of operation of an asynchronous generator with a short-circuited rotor as part of a wind turbine, which makes it possible to provide power to the alternating current network at low wind speeds.

Compatibility and thermokinetics studies of 4-amino triazolium picrate with various polymers

Compatibility and thermokinetics studies of 4-amino triazolium picrate with various polymers

Stability and compatibility of parenteral nutrition solutions; a review of influencing factors

Both stability and compatibility of parenteral nutrition solutions (PNS) with drug products are major concerns for clinicians and clinical pharmacists, especially when concurrent administration of PNS with intravenous medications (IVM) is unavoidable. Since the same physicochemical principles apply to both adult’s and paediatrics’ PNS, concerns about stability and compatibility may still apply to both. However, these concerns are relatively more common in paediatrics and neonatal clinical settings, where limited vascular access can be problematic and the coadministration of PNS and drugs is more common. In neonatal and paediatric populations, there have been few experimental studies and comprehensive evaluations looking at medication compatibility with frequently used PNS. This work is part of a larger research project concerned for compatibility of PNS with commonly used intravenous medication in paediatric and neonates. This paper captures and reviews published data on factors influencing stability and compatibility of parenteral nutrition solutions. This information will help clinicians and clinical pharmacists to understand the principals of the stability and compatibility of PNS, furthermore, it will inform better design of future compatibility studies, as it highlights the complexity of PNS and the multiple factors influencing the stability of PNS, and hence its compatibility with IVM. When preparing, prescribing, and administering the PNS, especially when co-administration with IVM is unavoidable, it is important to take into account the physicochemical properties of the PNS components and IVM as well as administration conditions and environmental factors. These factors should also be considered in the design of the compatibility studies of the PNS with the IVM.

Study of compatibility between a 3T MR system and detector modules for a second-generation RF-penetrable TOF-PET insert for simultaneous PET/MRI.

Simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) has shown promise in acquiring complementary multiparametric information of disease. However, designing these hybrid imaging systems is challenging due to the propensity for mutual interference between the PET and MRI subsystems. Currently, there are integrated PET/MRI systems for clinical applications. For neurologic imaging, a brain-dedicated PET insert provides superior spatial resolution and sensitivity compared to body PETscanners. Our first-generation prototype brain PET insert ("PETcoil") demonstrated RF-penetrability and MR-compatibility. In the second-generation PETcoil system, all analog silicon photomultiplier (SiPM) signal digitization is moved inside the detectors, which results in substantially better PET detector performance, but presents a greater technical challenge for achieving MR-compatibility. In this paper, we report results from MR-compatibility studies of two fully assembled second-generation PET insert detectormodules. We studied the effect of the presence of the two second-generation TOF-PET insert detectors on parameters that affect MR image quality and evaluated TOF-PET detector performance under different MRI pulse sequenceconditions. With the presence of operating PET detectors, no RF noise peaks were induced in the MR images, but the relative average noise level was increased by 15%, which led to a 3.1 to 4.2-dB degradation in MR image signal-to-noise ratio (SNR). The relative homogeneity of MR images degraded by less than 1.5% with the two operating TOF-PET detectors present. The reported results also indicated that ghosting artifacts (percent signal ghosting (PSG) ⩽ 1%) and MR susceptibility artifacts (0.044 ppm) were insignificant. The PET detector data showed a relative change of less than 5% in detector module performance between running outside and within the MR bore under different MRI pulse sequences except for energy resolution in EPI sequence (13% relative difference). The PET detector operation did not cause any significant artifacts in MR images and the performance and time-of-flight (TOF) capability of the former were preserved under different tested MRconditions.

FORMULATION AND EVALUATION OF FAST DISSOLVING TABLET OF LEVOCETIRIZINE DIHYDROCHLORIDE AND MONTELUKAST SODIUM

Introduction: Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Objective: The aim of the present study was to formulate fast-dissolving tablets of Levocetirizine dihydrochloride (LEV) and Montelukastsodium (MON) by direct compression method. Material And Methods: An attempt was made to mask the bitter taste of Levocetirizine by preparing an ion exchange resin complex by a batch method using Kyron T-104. The tablets were prepared using mannitol, microcrystalline cellulose as diluents, and croscarmellose sodium and crospovidone as super disintegrants. Parameters like a drug: resin ratio, pH & swelling time were successfully optimized to prepare the drug resin complex. The fast-dissolving tablets were characterized for various pre and post-compression parameters along with disintegration time, content uniformity, wetting time, in-vitro drug release, in vivo taste evaluation, and compatibility studies. Result and Discussion: The tablets prepared by direct compression method possess a hardness of 3.4 to 3.6 Kg/cm², percentage friability of 0.65 to 0.80, in vitro disintegration time of 29.82 to 51.7 seconds, and wetting time of 20.4 to 46.8 seconds. The formulation (F4)containing crospovidone and croscarmellose sodium in 2:4 ratios showed better disintegration time and more than 99% drug release within 6 minutes. Comparative taste evaluation proves the palatability of formulated tablets. Results of stability studies were also found in acceptable limits. Conclusion: The prepared orodispersible tablets disintegrate within seconds without the need for water and enhance absorption; thismay lead to increased bioavailability of LEV as well as MON.

FORMULATION DEVELOPMENT AND CHARACTERIZATION OF LAFUTIDINE RAFT SYSTEM

Objective: The present research work is focused to develop in situ raft gel of lafutidine. Sodium alginate is one of the critical components for the development in situ raft system. Methods: The formulation was prepared using hydrophilic polymers such as ethyl cellulose, HPMC K4M, and chitosan. The formulations were subjected to evaluation characteristics such as pH, in vitro gelling time, viscosity, density, gel strength, drug-polymer compatibility studies, drug content floating lag time, swelling index, and in vitro release studies. Results: The pH of all the prepared batches was found in the range of 5.7 to 7.6. All the prepared formulations showed viscosity in the range of 264 to 320 cps, with gelling time from 4-7 s. For F1-F15 batches Floating lag time was found to be in the range of 9-24 sec. Densities of all formulations stomach specific in situ gels were in the range of 0.4 to 0.8 gm/cm3. The highest swelling index was observed in F15 with 14.16% Highest gel strength is exhibited by F15; all the formulations were in the range of 95.46–99.95, indicating the uniform distribution of the drug. Formulation F15 containing chitosan in combination with ethyl cellulose gave the highest drug release of 99.78% and also showed sustained and controlled release for up to 24h. Conclusion: F15 shows an R2 value of 0.999. As its value is nearer to the ‘1’ it is confirmed as it follows the Zero order release with an ‘n’ value is 1.5021 for the optimized formulation (F15) i.e., the n value indicates super case II transport and is considered as optimized formulation.

A Mobile Self-Management App (CanSelfMan) for Children With Cancer and Their Caregivers: Usability and Compatibility Study.

Despite the increasing development of different smartphone apps in the health care domain, most of these apps lack proper evaluation. In fact, with the rapid development of smartphones and wireless communication infrastructure, many health care systems around the world are using these apps to provide health services for people without sufficient scientific efforts to design, develop, and evaluate them. The objective of this study was to evaluate the usability of CanSelfMan, a self-management app that provides access to reliable information to improve communication between health care providers and children with cancer and their parents/caregivers, facilitating remote monitoring and promoting medication adherence. We performed debugging and compatibility tests in a simulated environment to identify possible errors. Then, at the end of the 3-week period of using the app, children with cancer and their parents/caregivers filled out the User Experience Questionnaire (UEQ) to evaluate the usability of the CanSelfMan app and their level of user satisfaction. During the 3 weeks of CanSelfMan use, 270 cases of symptom evaluation and 194 questions were recorded in the system by children and their parents/caregivers and answered by oncologists. After the end of the 3 weeks, 44 users completed the standard UEQ user experience questionnaire. According to the children's evaluations, attractiveness (mean 1.956, SD 0.547) and efficiency (mean 1.934, SD 0.499) achieved the best mean results compared with novelty (mean 1.711, SD 0.481). Parents/caregivers rated efficiency at a mean of 1.880 (SD 0.316) and attractiveness at a mean of 1.853 (SD 0.331). The lowest mean score was reported for novelty (mean 1.670, SD 0.225). In this study, we describe the evaluation process of a self-management system to support children with cancer and their families. Based on the feedback and scores obtained from the usability evaluation, it seems that the children and their parents find CanSelfMan to be an interesting and practical idea to provide reliable and updated information on cancer and help them manage the complications of this disease.

Oral Gastroretentive Film of Lacidipine for the Treatment of Gastroparesis

The research work was aimed to formulate and evaluate gastroretentive mucoadhesive film of calcium channel blocker, Lacidipine for treatment of gastroparesis. Box-Behnken design was used for preparation of optimized formulation using solvent casting method. In this design, different concentrations of mucoadhesive polymers HPMC E15, Eudragit RL100, and Eudragit RS100 were considered as independent variables and its effect on responses like percent drug release, swelling index at 12 h, and folding endurance of the film were examined. Drug and polymer compatibility studies were performed using Fourier transform infrared spectroscopy and differential scanning calorimetry. Optimized formulation was evaluated for organoleptic properties, weight variation, thickness, swelling index, folding endurance, drug content, tensile strength, percent elongation, drug release, and percent moisture loss. The results revealed that the film possessed considerable flexibility and smoothness, and in vitro drug release was found to be 95.22% ± 0.93% at the end of 12 h. Scanning electron microscopy imaging of film displayed smooth, uniform, and porous surface texture. The dissolution followed Higuchi's model and Hixson Crowell model displayed non-Fickian drug release mechanism. Furthermore, the film was incorporated in capsule and the presence of capsule showed no effect on the drug release profile. In addition, no change was observed in the appearance, drug content, swelling index, folding endurance, and drug release upon storage at 25°C ± 2°C and 60% ± 5% relative humidity for 3 months. Collectively, the study revealed that gastroretentive mucoadhesive film of Lacidipine could serve as an effective and alternate site-specific targeted delivery in the management of gastroparesis.

A QBD WITH THE FRACTIONAL FACTORIAL DESIGN WAS USED TO MATCH THE SIMILARITY BETWEEN RANOLAZINE EXTENDED-RELEASE TABLETS 500 MG AND 1000 MG

Objective: Formulation and development of Ranolazine extended-release Tablets 500 mg and 1000 mg by using QBD with Fractional factorial design to match the similarity with Branded formulation (RANEXA®). Methods: Ranolazine extended-release tablets were developed by using various polymers, Polyquid PA100 and ETHOCEL TMstandard 7 premium and Hypromellose with a wet granulation process. QBD (Quality by Design) approach was used to identify the formulation and process variables that may affect the CQAs (critical quality attributes). Excipient compatibility studies were conducted to identify the interaction between API (active pharmaceutical ingredient) and selected excipients. Additionally, using a two-level, fractional factorial (22+3) design, the DOE (design of experiments) was employed to confirm the impacts of key process factors (fluid uptake and kneading time) on the formulation's ability to match the dissolution (f2) compared to RLD (reference listed drug) and establish a stable formulation. Results: Initial risk assessment was carried out to identify the various attributes such as API flow properties, solubility, PSD, Hygroscopicity, formulation, and process variables to impact the quality of the drug product. Flow properties of API indicate poor flow. Drug and excipients compatible study results indicate that excipients used in the compatibility study are considered compatible with the active ingredient. As per the saturation solubility studies and sink conditions, dissolution media was selected. Significant differences were found among the drug release profile by examining the various levels of polymers and binders. Using a two-level, fractional factorial (22+3) design, optimum process parameters were identified with selected formulation to match the dissolution (f2) similarity with the reference listed drug (RLD); finally, XRD (X-ray diffraction) studies confirm that the crystalline polymorphic forms (Form 1) peaks in optimum formulation (F07) comparable to the reference listed drug. Conclusion: Optimized formulation and process were established with QbD (quality by design) that provides the consistent drug release to match the f2 similarities with the extended-release tablets of RANEXA®(Ranolazine) 500 mg and 1000 mg.

Evaluation of ATBS Polymers for Mangala Polymer Flood

Summary Mangala field has been under polymer flood since 2015. The polymer flood has been more successful in accelerating recovery compared to waterflood. As the flood matured, field performance indicated that part of the injected polymer was degrading in the reservoir. Laboratory studies and polymer samples collected from the reservoir suggest that the most likely reason for the degradation is increased hydrolysis due to thermal aging. This degradation compels higher dosing of polymer to make up for the lost viscosity and increases operating costs. Polymer precipitation in the reservoir may also lead to loss of reservoir permeability. Literature surveys and preliminary laboratory studies showed that polymers with acrylamide-tertiary-butyl-sulfonic acid monomer units (referred to as ATBS polymers) could be a suitable option for Mangala. To evaluate the hypothesis, the team did a series of laboratory and coreflood studies. The studies include accelerated thermal ageing, rheology, dynamic adsorption, injectivity, waterflood with fresh and degraded samples, and compatibility studies with topside chemicals. Two hydrolyzed polyacrylamide (HPAM) polymers with different degrees of hydrolysis (DOH) and two ATBS polymers were evaluated. The selected ATBS polymer was then tested for compatibility with surface topside chemicals. The studies show that the classic 20 to 25% DOH HPAM suffers viscosity degradation and possible precipitation in Mangala reservoir conditions. ATBS polymers and a lower DOH HPAM provide superior results to the incumbent HPAM with an acrylamide (AM) (86)-ATBS (14) copolymer providing the best results. ATBS polymers were especially resistant to cloudpoint lowering and provide some superiority in shear degradation. The ATBS monomer was resistant to hydrolysis during the period of testing. Contrary to the published literature, ATBS polymers showed higher adsorption and their propagation through cores required a higher pressure drop. ATBS polymer seemed to plug a low-permeability section of the core stack. All polymers reach their peak viscosity at 30 to 40% hydrolysis and decline sharply after 40%, but viscosity and cloudpoints measured during accelerated aging are possibly conservative. A large-scale pilot of ATBS injection in Mangala is under way to validate the laboratory test results. ATBS polymer can be a suitable polymer for some layers of Mangala with a high residence time and permeability. The choice is driven by the economics of the incremental cost of ATBS for the benefits it offers. In some sands with shorter interwell spacing, a lower DOH HPAM may be a more cost-effective solution. The study results in this paper provide insights to operators to understand the reservoir performance of existing polymer floods and plan for future polymer floods.

SeDeM expert system with I-optimal mixture design for oral multiparticulate drug delivery: An encapsulated floating minitablets of loxoprofen Na and its in silico physiologically based pharmacokinetic modeling.

Introduction: A SeDeM expert tool-driven I-optimal mixture design has been used to develop a directly compressible multiparticulate based extended release minitablets for gastro-retentive drug delivery systems using loxoprofen sodium as a model drug. Methods: Powder blends were subjected to stress drug-excipient compatibility studies using FTIR, thermogravimetric analysis, and DSC. SeDeM diagram expert tool was utilized to assess the suitability of the drug and excipients for direct compression. The formulations were designed using an I-optimal mixture design with proportions of methocel K100M, ethocel 10P and NaHCO3 as variables. Powder was compressed into minitablets and encapsulated. After physicochemical evaluation lag-time, floating time, and drug release were studied. Heckel analysis for yield pressure and accelerated stability studies were performed as per ICH guidelines. The in silico PBPK Advanced Compartmental and Transit model of GastroPlus™ was used for predicting in vivo pharmacokinetic parameters. Results: Drug release follows first-order kinetics with fickian diffusion as the main mechanism for most of the formulations; however, a few formulations followed anomalous transport as the mechanism of drug release. The in-silico-based pharmacokinetic revealed relative bioavailability of 97.0%. Discussion: SeDeM expert system effectively used in QbD based development of encapsulated multiparticulates for once daily administration of loxoprofen sodium having predictable in-vivo bioavailability.

VITAMIN C AND CRANBERRY EXTRACT EFFERVESCENT TABLET FORMULATION, CHARACTERIZATION, AND EVALUATION

Background: Effervescent floating tablets are used oral dosage form, to enhance the patient compliance, drug bioavailability and to increase the absorption rate. Cranberry (Vaccinium macrocarpon), widely used as a preventive agent against urinary tract infections, also suggested for Type II diabetes, myalgic encephalomyelitis, scurvy, and as a diuretic pill for being rich in nutrients and anti-oxidant properties. Objectives: The aim of the study is to formulate and evaluate the effervescent tablets of Cranberry and Vitamin C. Methodology: As per defined criteria of US FDA, effervescent tablet as per composition is formulated by citric acid and sodium bicarbonate and intended to dissolve in water before administration. Active substance and excipient compatibility studies were done by UV and FTIR, resulted absence of any interaction. Pre-formulation studies including Bulk density, tapped density, angle of repose, Hausner’s ratio, Carr’s index and water content. Results: Formulations were evaluated for weight variation, thickness, hardness, pH of solution, drug dissolution time, content uniformity as defined specification of U.S.P and BP. Stability and storage condition studies were also monitored with average results of 96% drug assay and dissolution. All the results showed excellent formulation of tablet and flow properties of granules. Conclusion: Further studies required to approach targeted and spontaneous release of active as optimized effervescence maybe helpful in delivery of actives and enhancing patient compliance.

Application of D-Optimal Mixture Design in the Development of Nanocarrier-Based Darifenacin Hydrobromide Gel.

Darifenacin hydrobromide, a BCS Class II drug, is poorly bioavailable due to extensive first-pass metabolism. The present study is an attempt to investigate an alternative route of drug delivery by developing a nanometric microemulsion-based transdermal gel for the management of an overactive bladder. Oil, surfactant, and cosurfactant were selected based on the solubility of the drug, and surfactant: cosurfactant in surfactant mixture (Smix) was selected at a 1:1 ratio as inferred from the pseudo ternary phase diagram. The D-optimal mixture design was used to optimize the o/w microemulsion wherein the globule size and zeta potential were selected as dependable variables. The prepared microemulsions were also characterized for various physico-chemical properties like transmittance, conductivity, and TEM. The optimized microemulsion was gelled using Carbopol 934 P and assessed for drug release in vitro and ex vivo, viscosity, spreadability, pH, etc. Drug excipient compatibility studies showed that the drug was compatible with formulation components. The optimized microemulsion showed a globule size of less than 50 nm and a high zeta potential of -20.56 mV. The ME gel could sustain the drug release for 8 hours as reflected in in vitro and ex vivo skin permeation and retention studies. The accelerated stability study showed no significant change in applied storage conditions. An effective, stable, non-invasive microemulsion gel containing darifenacin hydrobromide was developed. The achieved merits could translate into increased bioavailability and dose reduction. Further confirmatory in vivo studies on this novel formulation, which is a cost-effective & industrially scalable option, can improve the pharmacoeconomics of overactive bladder management.

Compatibility Coreflood Studies Explore Formation Damage in Tight Reservoirs

_ This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper SPE 207764, “Case Study of Identifying and Minimizing Formation Damage in Tight Reservoirs Caused by Drilling Fluids in Abu Dhabi Onshore Operation Using Compatibility Coreflood Studies,” by Raymond Saragi, Mohammad Husien, and Dalia S. Abdullah, ADNOC, et al. The paper has not been peer reviewed. _ The authors examine formation-damage mechanisms caused by drilling fluids in tight reservoirs in several onshore Abu Dhabi oil fields. Three phases of compatibility corefloods were performed to identify the potential of improving hydrocarbon recovery and examine reformulated or alternate drilling muds and treatment fluids. The compatibility corefloods on tight reservoir cores, along with high-resolution quantifications and visualizations, identified damaging mechanisms and helped identify potential to improve hydrocarbon recovery and treatment-fluid options. Introduction The operator examined drilling-mud performance for UAE fields including Bab, Rumaitha, Qusahwira, Sahil, and Mender. Results appeared to be good in high-permeability zones but not in lower-permeability zones. A multiphase compatibility study consisting of a series of coreflood simulations analyzed both producer and injector wells, but the complete paper focuses on the producer wells. The use of nano-computed tomography (CT) scans and cryogenic scanning electron microscope (SEM) with energy dispersive spectroscopy (EDS) as interpretative tools provided insights into the coreflood results (55 of which are presented in the complete paper). The reservoirs consist of Lower Cretaceous carbonate sediments. This study examined lower-permeability zones; the results shown in the complete paper are only from the tight samples below 15 md. The samples used in the study are detailed in Table 1 of the complete paper and represented the following reservoirs: - Bab (wells coded BB-1, BB-2, BB-3, BB-4, BB-5, BB-6, and BB-7; 0.1–15-md gas permeability) - Mender (well coded MN-1; 3–12-md gas permeability) - Qusahwira (wells coded QW-1 and QW-2; 0.5–1-md gas permeability) - Rumaitha (well coded RA-1; 2–15-md gas permeability) - Sahil (well coded SA-1; 2–4-md gas permeability) Methodology Coreflood simulations were performed using specialized equipment capable of executing the study at reservoir conditions while eliminating artifacts such as corrosion. Accurate replication of reservoir conditions is important, especially where potential scaling exists. Phase 1 examined permeability alterations and damaging mechanisms after application of the currently used drilling mud. The methodology is detailed in the complete paper, but the authors emphasize the use of interpretive tools in this process. Phase 2 examined a series of reformulated and alternate drilling muds. Following the results of Phase 1, the current field mud was reformulated and examined as Reformulated Mud Formulation 1 alongside three alternate drilling muds from separate vendors. Phase 3 built on Phases 1 and 2 by examining the incorporation of a displacement or treatment fluid as part of the operational sequence. The methodology for Phase 3 was similar to that used in the previous phases, with the addition of treatment-fluid application before drawdown.

용융압출법을 이용한 서방출형 임플란트의 개발 및 평가

In this study, poly(lactic-co-glycolic acid) (PLGA)-based subcutaneous implant containing metformin HCl was prepared by hot-melt extrusion (HME). This study aimed to evaluate swelling and dissolution behavior for application as subcutaneous implant. Implants containing metformin HCl were fabricated successfully at 30 rpm, 90oC by HME. Drugexcipient compatibility studies through FT-IR and DSC revealed the absence of any interaction between the drug and polymers. Dissolution rate and swelling ratio of metformin HCl was significantly affected by the type of PLGA. Dissolution rate increased as the ratio of -COOH terminal group and GA. By the results, we could confirm that the mechanism of drug release from implants is Korsmeyer-Peppas model (n=0.14~0.71) by combination of non-fickian diffusion and erosion. The formulation F7 with 65% of RG 752H and 5% of RG 502 was showed excellent swelling ratio with drug release control. In this study, mixing 5~10% of RG 502 with RG 752H can be expected to develop optimal implants exhibiting diffusion-controlled release for 3 months without initial burst release.

Formulation Variables Effect on Gelation Temperature of Nefopam Hydrochloride intranasal in Situ Gel (Conference Paper) #

Nefopam (N.F.) HCl is a non-narcotic centrally-acting, non-opioid benzoxazocine analgesic to relieve acute and chronic pain. It exhibits low bioavailability (about 36%) due to its first-pass degradation in the liver.
 Intranasal administration has been used as a new route for targeting active brain sites and enhancing the bioavailability of N.F. HCl bypassing hepatic metabolism.
 In situ gel of N.F. HCl was prepared by the cold method using different concentrations of Poloxamer 407, Poloxamer 188, HPMC K4M, Carbapol 934, and Hyaluronic acid polymers.
 The results show that identification tests are superimposed with references, solubility study shows that N.F. HCl is suitable to be administered intranasally; Compatibility studies reveal incompatibility of Nefopam HCl with HPMC K4M and Carbapol 934; meanwhile, no interaction with Methylcellulose and Hyaluronic acid.
 In conclusion, the obtained results revealed the incredible ability of the produced N.F. HCl intranasal in situ gel is intended to enhance drug bioavailability bypassing the metabolizing effect of the liver that N.F. HCl is facing when given orally.