Methocel K4M Research Articles

Formulation design and optimization of sustained release tablet dosage form of Diacerein

Diacerein is both an anti-inflammatory drug and an anti-arthritic agent. At present, no sustained release dosage form of Diacerein is commercially available. The aim of the study was to develop an optimized formulation of sustained release tablet dosage form of Diacerein that will be highly patient compliant. A three-level full factorial design was employed to develop nine different formulations of matrix tablets using a combination of Methocel K100M CR and Methocel K4M CR polymer at different ratios. The physical evaluation of both the drug-excipient powder mixtures and tablets of the nine formulations were performed and results were found to be within acceptable ranges for all tests. Dissolution profiles of tablets were obtained and the kinetics of drug release from the matrix tablets were determined by employing various mathematical models. The release data were simulated in Design Expert Software to carry out statistical analysis and the effect of both polymers on release patterns were observed after 1, 4 and 8 h in terms of contour plots and 3D surface plots, which were found to be statistically significant (p < 0.05). Finally, the overlay plot was obtained from which the optimized formulation of Diacerein was determined.

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.

SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™.

The study is based on using SeDeM expert system in developing controlled-release tramadol HCl osmotic tablets and its in-silico physiologically based pharmacokinetic (PBPK) modeling for in-vivo pharmacokinetic evaluation. A Quality by Design (QbD) based approach in developing SeDEM-driven full factorial osmotic drug delivery was applied. A 24 Full-factorial design was used to make the trial formulations of tramadol HCl osmotic tablets using NaCl as osmogen, Methocel K4M as rate controlling polymer, and avicel pH 101 as diluent. The preformulation characteristics of formulations (F1-F16) were determined by applying SeDeM Expert Tool. The formulation was optimized followed by in-vivo predictive pharmacokinetic assessment using PBPK “ACAT” model of GastroPlus™. The FTIR results showed no interaction among the ingredients. The index of good compressibility (ICG) values of all trial formulation blends were ≥5, suggesting direct compression is the best-suited method. Formulation F3 and F4 were optimized based on drug release at 2, 10, and 16 h with a zero-order kinetic release (r 2 = 0.992 and 0.994). The SEM images confirmed micropores formation on the surface of the osmotic tablet after complete drug release. F3 and F4 were also stable (shelf life 29.41 and 23.46 months). The in vivo simulation of the pharmacokinetics of the PBPK in-silico model revealed excellent relative bioavailability of F3 and F4 with reference to tramadol HCl 50 mg IR formulations. The SeDeM expert tool was best utilized to evaluate the compression characteristics of selected formulation excipients and their blends for direct compression method in designing once-daily osmotically controlled-release tramadol HCl tablets. The in-silico GastroPlus™ PBPK modeling provided a thorough pharmacokinetic assessment of the optimized formulation as an alternative to tramadol HCl in vivo studies.

Formulation and Evaluation of Posaconazole Bilayer Delayed Release Tablets Using Solid Dispersion Technique

The aim of present investigation to formulate bilayer tablets of posaconazole by using solvent evaporation technique. Posaconazole belongs to BCS class 2 which has high permeability and low solubility. In order to enhance the solubility of posaconazole solvent evaporation technique was applied where HPMC AS was used as carrier. This tablet consist of two layers of which first layer serves as loading dose which produce immediate release of drug and second layer serves as maintenance dose that provide controlled release of drug. The whole bilayer tablet is coated with Eudragit L30D55 to produce delayed release and protect drug from acid environment in stomach. The drug excipient compatibility study was performed by FTIR and no interaction was found. Croscaramellose was used in immediate release layer as superdisintegrant. Methocel K100M and Methocel E5M are used for sustain drug release in control release layer. The powder blend for evaluated for flow properties like angle of repose, bulk density, tapped density, Carr’s index and Hausner’s ratio which showed good results. Invitro dissolution studies was performed with USP dissolution apparatus 2- Paddle type. Invitro dissolution was performed for 2 hours in 0.1N HCl which showed no drug release followed by 6.8 phosphate buffer for 12 hours. The bilayer tablet showed initial release to provide loading dose of drug followed by controlled release up to 12 hours. Change in concentration of polymer and superdisintegrant showed impact on drug release profile. Increase in concentration of superdisintegrant in immediate release layer showed increased % drug release. Whereas increase in sustain release polymers in controlled release layer showed decrease % drug release. F9 batch showed satisfactory release up to 100% for 12 hours and was selected as best formulation. Reproducible batch for F9 was formulated and called F10 which also showed satisfactory results.

Formulation Development, Evaluation and Statistical Optimization of the Release Rate of Oral Sustained Release Matrix Tablet of Aceclofena

Aim: This work aimed to develop a sustained released hydrophilic matrix tablet of Aceclofenac for better therapeutic action. &#x0D; Background: Conventional dosage form didn't provide the desired level of drug release. Even many-marketed sustained-release tablets didn't always meet the satisfactory level of drug release. It was a challenging job for pharmaceutical scientists to develop a well-sustained release formulation. Keeping this perspective in mind a robust sustained release formulation was designed, developed and optimized with nontoxic, inert viscoelastic, semisynthetic polymers which will be accepted worldwide.&#x0D; Objective: The objective of this research was to develop an Aceclofenac sustained released matrix tablet, which will deliver the desired level of drug release.&#x0D; Method: Aceclofenac sustained released tablet was prepared with Methocel K-100M Premium (Hydroxypropyl Methylcellulose) and Unigel 270 (Pregelatinized starch). These two excipients were selected as independent formulation variables with three separate levels (high, intermediate and low). Nine batches of hydrophilic matrix tablets of Aceclofenac were prepared according to the 32 Factorial Design with an average weight of 365 mg/tablet. Each prepared batch of tablets was then evaluated for drug content, physical parameters and drug release. Mathematical models were then generated using Analysis of Variance employing Design-Expert Software version 8.0.7.1 for % cumulative release at T1 hr, T4 hr and T7 hr. FTIR spectroscopy was carried out to evaluate drug-excipients interaction after formulation.&#x0D; Results: Design-Expert Software after analyzing the release data of prepared 9 batches provides an optimized composition of formulation. The optimized batch showed desirable results for cumulative % release (CPR)T1hr, CPR T4hr and CPR T7hr are 35.61, 52.16 and 61.98 respectively. &#x0D; Conclusion: Application of statistical experimental design, the physicochemical studies and the in vitro-release study, the mathematically predicted formulation and its manufacturing and validation of aceclofenac sustained-release tablets showed great advancement from the trial-and-error method of development of sustained-release drug delivery systems.

Development of a Transdermal Delivery System for Tacrine

Tacrine has several mechanisms of action. The putative primary mechanism of action of tacrine for Alzheimer's disease is reversible inhibition of acetylcholinesterase (AChE), which thus slows the breakdown of the chemical messenger acetylcholine (ACh) in the brain. Tacrine also inhibits butyrylcholinesterase activity. In accumulation, tacrine blocks sodium and potassium channels. Tacrine also acts as a histamine N-methyltransferase inhibitor. This study was carried out to develop matrix based transdermal patches containing Tacrine to overcome the first pass metabolism and to reduce frequency of dosing compared to oral route. . Matrix type of transdermal patches was developed by using Methocel K4M, Methocel K15M, Methocel K100M and Xanthan gum polymers. Transdermal patches were prepared by employing solvent casting method. Drug excipients compatibility studies were carried out by using FTIR, and it was observed that there were no interactions. Formulations were prepared with the varying concentrations polymers ranging from F1-F16, and all the formulations were evaluated for various physical parameters Physical appearance, Flatness, Weight variation, Thickness, Folding endurance, Drug content, Moisture uptake, Moisture content and Swelling study and all the results were found to be within the pharmacopeial limits, invitro drug release studies by using dialysis membrane. Among all the 16 Tacrine transdermal patches formulations F5 formulations which contain Methocel K15M 100 mg had shown 97.61% % cumulative drug release within 12 hours.

Assessing compatibility of excipients selected for a sustained release formulation of bilberry leaf extract

The study is aimed to assess the compatibility of bilberry leaf powder extract (BLPE) with six excipients selected for sustained-release (SR) tablet formulation. The BLPE was obtained with the addition of L-arginine and Myo-inositol as the carriers. Thermogravimetric (TG-DTG) analysis and Fourier-transform infrared spectroscopy (FTIR), supported by Pearson correlation analysis, were applied to detect possible interactions in the binary mixtures (1:1) of the BLPE with each excipient. The TG-DTG showed some deviations in the thermal behavior of the BLPE / excipient mixtures. However, only the thermal behavior of magnesium stearate in the mixture significantly differed from individual samples, which suggested chemical interaction for this excipient. The FTIR analysis confirmed that the BLPE is compatible with Eudragit L100, Methocel K4M, Methocel K100LV, Avicel PH-101, and Plasdone S-630. Whereas it undergoes solid-state chemical interaction in the binary mixture with magnesium stearate. According to the FTIR-spectra, it is suggested that this interaction results in the formation of stearic acid and alkalization of the medium. These findings evidence for the possibility of using TG-DTG analysis as an independent thermal technique for compatibility studies and also confirm the earlier reported interaction of basic lubricants, e.g., stearic salts, with active ingredients containing amino groups.

Prediction of the composition of prolonged release tablets based on 4,4'-(propandiamido) sodium dibenzoate using the SeDeM method

Introduction. Direct compression technology is one of the most common tablet technologies. As known, many active pharmaceutical ingredients are not suitable for this technology without the addition of special excipients. A useful tool for determining the suitability of powdered materials for direct compression technology is the Sediment Delivery Model (SeDeM) method, based on the concept of Quality by Design. The presented method allows not only to assess the suitability of a material for direct compression, but also helps to predict the composition of a solid dosage form in the form of a tablet, which, in turn, leads to a significant reduction in experimental work carried out in the development of a new drug.Aim. Prediction of the compositions of matrix tablets based on sodium 4,4'-(propanediamido)dibenzoate with prolonged release, obtained by direct compression using the method of mathematical modeling SeDeM.Materials and methods. The objects of the study were the original substance sodium 4,4'-(propanediamido)dibenzoate, as well as a number of auxiliary substances, which included polymers used for dosage forms with prolonged release, a dusting component – magnesium stearate, and a filler – lactose monohydrate. Physicochemical and technological properties of APIs, explosives, obtained tablet mixtures and tablets were studied in accordance with the requirements of the State Pharmacopoeia of the Russian Federation XIV ed. and EP 9th ed.Results and discussion. The properties of the substance and excipients were assessed in accordance with the SeDeM method. It was found that the substance 4,4'-(propanediamido) sodium dibenzoate is not suitable for direct pressing due to poor flowability and low compressibility. Hypromellose Methocel K4M had good compressibility, but it did not have sufficient flowability. The other tested polymers had satisfactory properties for the direct compression technology. The composition of the tablet mixtures was calculated using the SeDeM method, the obtained tablet mixtures had satisfactory technological characteristics for obtaining tablets by direct compression. The tablets obtained as a result of the experiment also met the pharmacopoeial requirements.Conclusion. Prediction of the composition of sustained-release tablets based on the original substance sodium 4,4'-(propanediamido)dibenzoate was carried out using the SeDeM method. It was found that this method is suitable for the development of the composition of tablets based on sodium 4,4'-(propanediamido)dibenzoate.

In situ Gels of Acylovir Nanoemulsions for Improved Delivery to the Eye

Background: Acyclovir, BCS Class III drug is commercially available as 3% w/w eye ointment for multiple applications. Acyclovir nanoemulsions can be proposed to reduce dose because of improved permeation characteristics. Further, the development of in situ ophthalmic gels can be advantageous to reduce the number of applications due to increased mucoadhesion and sustaining effect. Objective: The purpose of this study was the development and evaluation of nanoemulsions based in situ gels of Acyclovir (1% w/w) as potential ophthalmic delivery systems. Methods: Nanoemulsions of Acyclovir were developed by Phase Inversion Temperature method using Capmul MCM, stearyl amine and Kolliphor RH 40 as liquid lipid, charge inducer and surfactant, respectively selected on the basis of Acyclovir solubility in the oil phase and emulsification ability of surfactants. These nanoemulsions were further developed into in situ ophthalmic gels using gellan gum and Methocel K4M. Results: The developed gels showed a sustained effect in vitro release studies and improved goat corneal permeation in ex vivo studies when compared to marketed ointment. HET-CAM studies concluded the absence of irritation potential, while in vivo irritation study in Wistar rats showed the absence of erythema and swelling of eyes after visual inspection for 72 hours. Histopathological studies on isolated rat corneas showed no abnormalities in anterior corneal epithelium and corneal stroma without any epithelial hyperplasia. Acyclovir nanoemulsions based in situ ophthalmic gel showed increased corneal deposition and permeation in isolated rat eyes. Conclusion: The improved potential of developed ophthalmic gels was proven due to the reduced frequency of application compared to the marketed ointment in animal studies.

Ketorolac Tromethamine for Sustained Ocular Delivery; Novel In-Situ Gels Development and Evaluation

Objective: Ophthalmic ketorolac is used to treat itchy eyes caused by allergies. It also is used to treat swelling and redness (inflammation) that can occur after cataract surgery. Ketorolac is in a class of medications called nonsteroidal anti-inflammatory drugs (NSAIDs).&#x0D; Methods: Ocular bioavailability is always poor from conventional ophthalmic drops due to spillage and nasolachrymal drainage. Ocular in situ gels can increase the drug residence time thus increasing bioavailability. Polyacrylic acid (Carbopol 934) was used as the gelling agent in combination with hydroxypropylmethylcellulose (Methocel K4M) which acted as a viscosity enhancing agent. Compatibility studies of the drug excipients were carried out using differential scanning calorimetry. The prepared formulations were characterized for clarity, pH, drug content, sol-to-gel transition by scanning electron microscopy, in-vitro and in-vivo drug release, ocular irritation and stability.&#x0D; Results: FTIR spectras revealed that, there was no interaction between LEV and excipients. The formulated gels were transparent, uniform in consistency and had spreadability with a pH range of 7.1 to 7.4. Rheological studies revealed that the formulations were psuedoplastic in nature, drug content of sterile in situ gels was found to be 92-98%.Release kinetic study showed that the formulation followed first order diffusion controlled and the optimized formulations was having good antibacterial efficacy.&#x0D; Conclusion: The said promising formulation (F4) would be able to offer benefits such as increase residence time, prolonged drug release, reduction in frequency of administration and thereby definitely prove to improve the patient compliance.&#x0D;

TOPICAL GEL OF EXTRACT OF MANGIFERA INDICA L. SEED KERNELS; AN INDIGENOUS PLANT WASTE FOR POTENTIAL ANTI-ACNE ACTIVITY

The present study was aimed at the development of topical gel of extract of Mangifera indica L. seed kernel and evaluation of its in vitro antibacterial activity. Various extracts using different solvents were prepared and evaluated for in vitro activity against Propionibacterium acnes. Ethanolic extract of M. indica L. seed kernel exhibited the highest in vitro antimicrobial activity and was considered further. Topical gels of this ethanolic extract were prepared using different polymers such as Carbopol 974P, Xanatural 180 and Methocel K15M in varying concentrations. The topical gel of 10 % w/w ethanolic extract of M. indica L. seed kernel with 2% w/w Carbopol 974P was uniform and yellowish transparent with satisfactory spreadability. The developed gel showed greater in vitro antimicrobial activity as compared to marketed herbal cream. These results indicate the potential of topical gel of ethanolic extract M. indica L. seed kernel as anti-acne formulation developed from plant waste product.

Design and Evaluation of Press Coated Formulation of Aceclofenac and Comparison with Marketed Preparations.

The primary objective of the studies is to investigate whether compression coating could be used to produce tablets providing maximum drug plasma concentration 6 to 8 hours after an evening dose taken at approximately 22:00. Fast Dispersible core tablets containing Aceclofenac were prepared using super disintegrants like Ac-Di-Sol, Crospovidone, and Sodium starch glycolate through wet granulation method and evaluated for various parameters. Prepared press-coated tablets were characterized for physical parameters, drug content, lag time, in vitro drug release characteristics. Aceclofenac formulation tablets of batch F4 containing combination Methocel K4M and Methocel K100M showed desired lag time along with drug release as compared to other formulations. The Comparative dissolution study of an optimized formulation containing Aceclofenac was carried with marketed preparations also showed good results.

Analysis on the evaluation of aceclofenac bilayer tablets and its formulation using FT-IT method

The detached of the current research progress a bilayer tablet of aceclofenac utilizing sodium starch glycolate (SSG) and croscarmellose sodium (CCS) as super disintegrants for the formulation of immediate-release layer whereas polymers such as methocel K15M, Lubrizol 971P were utilized by the formulation of sustaining layer. The tablets were equipped by straight density technique. The organized tablets were estimated for pre-compressed parameters like micromeritic properties and post compressed parameters like bulk variation, aceclofenac satisfied and in-vitro dissolution studies. The in-vitro dissolution studies showed about 86.78 % of aceclofenac release from the bilayer tablet, indicating that a preliminary burst release of aceclofenac followed by sustaining action up to 12 h by the sustained layer of the tablets. In-Vitro kinetic data revealed that all the formulations surveyed the Higuchi prototype via fickian dispersal as announcement device subsequently the preliminary rupture announcement. FT-IR studies exposed here is no communication among the drug and polymers utilized in the study. The errand of medication is to safeguard and reestablish wellbeing and to soothe languishing. In this context, the most commonly used pain-relieving agent is aceclofenac an NSAID. In the present investigation, aceclofenac bilayer tablets were prepared to provide sustain effect for better therapeutic effect. These points of interest, clarify the requirement for the planning of changed medication conveyance framework.

Formulation and In vitro Release Behavior of Hydroxypropyl Methylcellulose (HPMC) Matrix Tablet Containing Poorly Soluble Fenofibrate

Fenofibrate, a water insoluble drug was used to prepare matrix tablet with four different viscosity grades of Hydroxypropyl Methylcellulose (HPMC) which were Methocel K4M CR, Methocel K15M CR, Methocel K100M CR and Methocel K100LV CR. The concentration of those excipients was 5, 10, 20, and 40% (w/w), respectively. The content of drug in a fixed quantity of powder in every formulation was ranged between 96.47 to 104.78 %. The dissolution study was done by using USP dissolution apparatus II. The kinetics of release was analyzed by using zero-order, first order, Korsmeyer-Peppas, Higuchi and Hixon-crowell equations to explain the drug release mechanism from the matrix tablets. In-vitro dissolution profile of matrix tablets were dependent upon the HPMC concentration and dissolution was rapid for tablets containing lower polymer proportion i.e. 5,10, and 20% Percentage (w/w) HPMC than those containing 40% (w/w) HPMC. Bangladesh Pharmaceutical Journal 23(1): 10-16, 2020

Carvedilol Matrix Tablet: Formulation and In Vitro Assessment

The present study was conducted for preparing and assessing different in-vitro characteristics of hydrophilic polymer based matrix tablets of carvedilol. Nine formulations of matrix tablet were prepared using three hydrophilic polymers having 1% of three different dissolution enhancers. The matrix formers were sodium-carboxy methyl cellulose, Methocel K4M CR, Methocel K100M CR and the dissolution enhancers were PEG 6000, Poloxamer 188 and Kollidon-CLSF. Formulations F-10, F- 13 and F-16 contained PEG 6000 as dissolution enhancer, formulations F-11, F-14 and F-17 contained Poloxamer 188 and formulations F-12, F-15 and F-18 contained Kollidon-CLSF. Tablet granules were evaluated for bulk density (0.293 ± 0.012 to 0.310 ± 0.004 g/ml), tapped bulk density (0.368 ± 0.013 to 0.380 ± 0.012 g/ml) and compressibility index (16.612 ± 1.868 to 22.834 ± 5.426). The data indicated satisfactory flow properties of granules during compression. The tablets were subjected to thickness (1.79±0.04mm), hardness (11.46 ± 1.06 kg/cm), and friability (0.26 ± 0.06%) measurements. The in vitro dissolution study was carried out for 12 hrs using USP type II dissolution apparatus in 6.8 buffer as the dissolution medium where release mechanisms were subjected to zero order, first order, Korsmeyer-Peppas, Hixson-Crowell and Higuchi kinetic studies. The order of dissolution enhancing power was PEG 6000 &gt; Poloxamer 188 &gt;Kllidon-CLSF. The drug release from the tablets followed erosion mechanisms. Among all the formulation F-13, F-14 and F-17 exhibited USP complied in vitro dissolution profiles. Bangladesh Pharmaceutical Journal 23(1): 26-31, 2020

Novel user-friendly night care spray to manage skin darkening.

Hyperpigmentation can be either diffused or localized. In treating diffused hyperpigmentation, larger surface area coverage is the requirement. Novel user-friendly spray formulation loaded with depigmenting agents can cater the night time need in treating skin darkening. Kojic acid and arbutin, the selected actives for the study exhibit low permeability and high irritancy generating hurdles in topical delivery. The aim of this study was to develop novel kojic acid and arbutin-loaded spray formulation as a night care product. "Thermosensitive gel spray" was fabricated by simple industry feasible cooling technique and evaluated for its ability to improve skin retention, penetration, improved anti-tyrosinase activity, and suppressed dermal irritancy. Comparative in-vitro and ex-vivo release profile showed the marked effect of poloxamer 407 and Methocel K100M in improving penetration and extending release over longer time period. Retention of actives in the skin layer was found to be eight times more in case of thermosensitive gel spray as compared to conventional gel formulation. The thermosensitive gel spray was free from any dermal irritancy and had higher tyrosinase inhibitory effect as against conventional gel. Furthermore, thermosensitive gel spray exhibited good stability and did not show any change in morphology and drug content during the 3-month storage. Kojic acid and arbutin-loaded thermosensitive gel spray can prove to be a promising strategy to treat hyperpigmentation.

Preparation and In-vitro Characterization of Gastroretentive Floating Tablets of Domperidone

The present investigation was design for domperidone floating table preparation and in-vitro characterization. The ultimate target was increasing gastric retention by means of floatability of the tablet. Hydrophilic cellulosic polymers, Methocel K15M and Methocel K100M were used in this experiment for achieving release controlling property. Sodium bicarbonate played the key role of floatation by generating gas. Direct compression was the method of choice for preparing the tablets. The tablets were evaluated for physical parameters, buoyancy study, total floating time determination and dissolution study. Acidic dissolution medium (0.1N HCl), mimicking the environment of the stomach, was used in USP II apparatus for 12 hours to find out the pattern of drug release. The release mechanism was analyzed by exploring the zero order, first order, Higuchi and Korsmeyer equations. All the physical parameters were within acceptable range and Methocel K100M showed more floating lag time and sustained release property than Methocel K15M. All the formulations showed more than 12 hours floating time. Fourier Transform Infrared Spectroscopy (FTIR) study confirmed the compatibility of the drug with the excipients. Bangladesh Pharmaceutical Journal 22(2): 170-175, 2019

Design of Experiment (DoE) Approach to Prepare, Characterize and Optimize the Gastroretentive Mucoadhesive Microspheres of Repaglinide

In this present investigation, gastroretentive mucoadhesive microspheres of Repaglinide was formulated, characterized and optimized by applying the design of experiment (DoE) for better release profile and sustain action of the drug. Solvent evaporation technique was used to prepare microspheres, where Methocel K15M CR (X1), Eudragit L 100 (X2) and rpm (X3) were used as independent variables whereas percent cumulative drug release at 8 hours (Y1), bond strength (Y2) and swelling at 8 hours (Y3) were used as dependent variables. Particle size, surface morphology, mucoadhesive bond strength, swelling study, and drug entrapment efficiency were determined to characterize the prepared microspheres. In vitro dissolution study was performed in 0.1N HCl (pH 1.2) media for 8 hours. Response surface of dependent variables was calculated by design expert software and it was found that most of the responses were fitted to the quadratic model. Percent cumulative drug release at 8 hours was found minimum 61.34% and maximum 87.29%, the minimum and maximum range of mucoadhesive bond strength was found 426.02 to 13335.74 N/m2 and in case of swelling at 8 hours, it was found 157.43 and 230.22%. After analyzing the responses, proposed formula was obtained from which minimization of percent cumulative drug release at 8 hours as well as swelling and maximization of bond strength was obtained. Thermal behavior was investigated by DSC study and no interaction was found between drug and excipients from FTIR study. Bangladesh Pharmaceutical Journal 22(2): 135-145, 2019

Development and Optimization of Acyclovir Loaded Mucoadhesive Microspheres by Box – Behnken Design

The grail of the study was to design, develop and characterize sustained release mucoadhesive microspheres of acyclovir and to optimize the drug release profile using response surface methodology by applying Box–Behnken design (BBD) which was equipped with three levels and three factors. Microspheres were prepared from Methocel K15M and Ethocel Standard 45 Premium using the emulsification solvent evaporation technique. The independent factors were the amounts of Methocel K15M (X1), amount of Ethocel Standard 45 Premium (X2), and RPM (X3). The dependent variables were cumulative percentage drug release (CDR) at 8 hour (Y1), bond strength (Y2), and swelling at 4 hour (Y3). To understand the effects of different factor level combinations on the responses, various response surface graphs and contour plots were prepared. Predicted values and experimental values for optimized formulation (X1 = 600 mg, X2 = 500 mg, and X3 = 336.57) was found to be in close agreement.&#x0D; Dhaka Univ. J. Pharm. Sci. 18(1): 1-2, 2019 (June)

Influence of different viscosity grade cellulose-based polymers on the development of valsartan controlled release tablets

This work is based on formulating and optimizing controlled release (CR) valsartan (160 mg) tablets using different viscosity grades of the cellulosic polymer. The objective was to develop an effective once-daily drug delivery system of this cardiovascular agent. Central composite design was used for designing the formulations. Polymers used were Methocel® K4M, K15M and K100M. Compatibility of excipients with active was studied through FT-IR. Micromeritic properties were determined and formulations exhibiting appropriate flow characteristics were compressed. Swelling behavior and in vitro buoyancy effect were studied and response surface curves were constructed to optimize the formulation. Multi-point dissolution profiles of valsartan CR tablets at pH 1.2, 4.5 and 6.8 were obtained. Model-dependent and model-independent methods were performed including f2, stability test as per ICH guidelines and ANOVA. FT-IR studies revealed the compatibility of valsartan with all excipients. Formulation K4T9 (containing 25% K4M polymer) was selected to be the best optimized trial, based on physical properties and controlled release profile (23% at 4 h, 82% at 16 h and 100% at 24 h). Results of buoyancy and swelling behavior indicated that HPMC-K4M polymer exhibited excellent floating lag time and swelling indexes. In vitro drug release kinetics showed that formulation K4T9 displayed Korsmeyer–Peppas drug release pattern with r value > 0.99. The manufacturing process of K4T9 was also found to be reproducible with a shelf life period of 41 and 36 months at room temperature and accelerated conditions, respectively. Valsartan CR matrix-based formulation was successfully prepared with Methocel K4M retardant.