Sustained release matrix tablet of 100 mg losartan potassium: Formulation development and in vitro characterization

Abstract Sustained release matrix tablets of 100 mg losartan potassium HCl were fabricated with two release retarding polymers namely HPMC K100 M and affinisol by direct compression method. Nine trial formulations were prepared by varying content of these polymers, each from 50 mg to 100 mg; keeping the total weight of the tablet 310 mg. The best formulation was selected based on in vitro drug release profile for 12 hours conducted in Type II dissolution apparatus at 50 rpm and water as dissolution medium. Pre-compression parameters such as bulk density, tap density, Carr's index and Hausner ratio were evaluated for the selected tablet. The tablets were subjected to thickness, weight variation test, drug content, hardness and friability. Drug release kinetics, surface morphology and accelerated stability study were investigated for that selected formulation. Formulation F4 with the composition of 75 mg HPMC K100M and 100 mg affinisol was selected as the best formulation that extended the drug release up to 12 hours. Pre-compression parameters and other tableting properties were within the Pharmacopoeia limit. Release kinetics analysis proved non-fickian zero-order drug release and that was further confirmed by surface morphology of the tablets before and after dissolution study visualized by SEM. The developed formulation was found to be stable for one month stored at 60 ○C.

A comparative physicochemical and pharmacological evaluation of dexamethasone sodium phosphate and betamethasone sodium phosphate mucoadhesive gels for the treatment of oral submucous fibrosis in rats

Abstract The present study is aimed to formulate steroidal oral mucoadhesive gels of dexamethasone sodium phosphate and betamethasone sodium phosphate. Six gel formulations each of dexamethasone sodium phosphate and betamethasone sodium phosphate prepared using two different polymers carboxymethyl cellulose sodium and hydroxypropyl methylcellulose, in variable proportions. All the formulations subjected for assessment of various physicochemical parameters and mechanical properties. The formulations BSP5 and DSP5, both containing 1.25 % carboxymethyl cellulose sodium, 1.25 % hydroxypropyl methylcellulose, exhibiting mucoadhesive strength of 12.300 ± 0.004 and 12.600 ± 0.01, adhesiveness of 28.04 ± 00 and 30.02 ± 00, cohesiveness of 28.04 ± 00 and 30.02 ± 00, drug release of 86.869 ± 0.380 % and 88.473 ± 0.457 % respectively were considered as promising ones and were further subjected for stability studies and in vivo study in male albino rats. Formulation DSP5 upon oral application for 4 months in arecoline induced oral submucous fibrosis rats, showed more than 80 % reduction in fibrosis as compared with BSP5 which showed nearly 50 % reduction. These results were concluded on the basis of histopathological profile and weight gain among the experimental animals during in vivo study. Hence, DSP5 by minimizing the painful injuries and morbidities justifies being suitable noninvasive model for OSMF treatment.

Formulation, Optimization, in vitro and in-vivo evaluation of levofloxacin hemihydrate Floating Tablets

Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.

Formulation And Evaluation Of Chlorothalidone Loaded Mouth Dissolving Film-A Bioavailability Enhancement Approach Using Multilevel Categoric Design

Objective: The intension of the present study includes fabrication and optimization of mouth dissolving film loaded with Chlorothalidone by solvent evaporation techniques using two components and their three levels as multilevel Categoric design. Methods: Major problem associated with the development of film loaded with BCS class II drug is to increase its solubility. Here the Chlorothalidone solubility achieved by co-solvents, such as methanol. After dissolving the drug in co-solvent, this drug solution is poured into an aqueous dispersion of Hydroxypropyl Methylcellulose E5 (HPMC E5) and Polyethylene glycol 400 (PEG 400). The two independent variables selected are factor A (concentration of HPMC E5) and factor B (concentration of PEG 400) was selected on the basis of preliminary trials. The percentage drug release (R1), Disintegration time in sec (R2) and folding endurance (R3) were selected as dependent variables. Here HPMC E5 used as a film former, PEG 400 as plasticizer, mannitol as bulking agent, Sodium starch glycolate as a disintegrating agent, tween 80 as the surfactant, tartaric acid as saliva stimulating agent, sodium saccharin as a sweetener and orange flavour etc. These fabricated films were evaluated for physicochemical properties, disintegration time and In vitro drug release study. Results: The formulation F6 has more favorable responses as per multilevel categoric design is % drug release about 98.95 %, average disintegration time about 24.33 second and folding endurance is 117. Thus formulation F6 was preferred as an optimized formulation. Conclusion: The present formulation delivers medicament accurately with good therapeutic efficiency by oral administration, this mouth dissolving films having a rapid onset of action than conventional tablet formulations.

Effect of precipitation inhibitors on pH-induced supersaturated phase behavior of dl-tetrahydropalmatine / 中草药

Objective: To investigate the effect of three types of precipitation inhibitors (PPI) HPMC K4M, HPMC AS MG and Soluplus on the pH-induced supersaturated phase behavior of dl-tetrahydropalmatine (dl-THP) at oral clinical doses. Methods: dl-THP pH solubility phase diagram and desaturation curve during pH-shift were drawn, and the solubility phase diagram was used to support dl-THP phase behavior. Area under the concentration-time curve and supersaturation ratio were used to analyze the effect of PPI on the phase behavior of dl-THP; Polarized light microscope and differential scanning calorimetry were used to analyze the precipitation properties. Results: Under the clinical dosage, the maximum supersaturation of dl-THP during the pH-shift was 3.93, and the supersaturation was lost over time; HPMC K4M, HPMC AS MG, and Soluplus could all maintain the supersaturation within 180 minutes during the pH-shift dissolution. HPMC K4M, HPMC AS MG, and Soluplus maintained supersaturation levels of 1.19, 1.89 and 1.36 respectively at a concentration of 5%, 1.30, 2.35 and 1.86 at a concentration of 20%, and 1.30, 2.60 and 2.07 at a concentration of 50%. Polarized light microscopy and differential scanning calorimetry results showed that crystalline precipitation occurred. Conclusion: All precipitation inhibitors can improve the pH-induced supersaturated phase behavior of tetrahydropalmatine, and this improvement behavior varies with the type and concentration of precipitation inhibitors. HPMC AS MG has the best effect.

Development of controlled release dexketoprofen tablets and prediction of drug release using Artificial Neural Network (ANN) modelling

Dexketoprofen trometamol (DT) is an active S (+) enantiomer of ketoprofen, and a non-steroidal anti-inflammatory agent. DT has a short biological half-life and the dosing interval is quite short when there is a need to maintain the desirable effect for longer time periods. Consequently, a controlled release DT tablet was designed for oral administration aiming to minimize the number of doses and the possible side effects. Calculations of the parameters for controlled release DT tablets were shown clearly. Controlled release matrix-type tablet formulations were prepared using hydroxypropyl methylcellulose (HPMC) (low and high viscosity), Eudragit RS and Carbopol, and the effects of different polymers on DT release from the tablet formulations were investigated. The dissolution rate profiles were compared and analyzed kinetically. An Artificial Neural Network (ANN) model was developed to predict drug release and a successful model was obtained. Subsequently, an optimum formulation was selected and evaluated in terms of its analgesic and anti-inflammatory activity. Although the developed controlled release tablets did not have an initial dose, they were found to be as effective as commercially available tablets on the market. Dissolution and in vivo studies have shown that the prepared tablets were able to release DT for longer time periods, making the tablets more effective, convenient and more tolerable.

Formulation and evaluation of a mucoadhesive buccal tablet of mefenamic acid

Buccal route of administration has many advantages such as improving patient compliance, bypassing the GIT and hepatic first pass effect. The objectives are to formulate mucoadhesive buccal tablet using Mefenamic acid and compatible excipients, and to evaluate the product using quality control tests and in vitro tests. The ingredients were subjected to Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy studies for compatibility test and the results showed no interaction. Two batches of mefenamic buccal tablet were prepared. The tablet thickness and diameter are 3.75 mm and 12 mm respectively. All tablets are within the specification of +/- 5%. The in-house tablet hardness is 6.8-15kg and percent friabilation is not more than 0.8%. The disintegration test showed that all tablets disintegrated within 4 hours. The content uniformity showed that tablets are within the range of 85%-115%. The tablet weight is within the 5% range. The percent swelling is 53.83% to 58.86% and moisture absorption is 14.79% to 15.56%. The surface pH of the tablet is close to the salivary pH, which means that it would not irritate the buccal mucosa. The buccal tablet has a mucoadhesiveness of 0.196 to 0.200. There was no change in pH and size after subjecting it to stability studies in human saliva. Drug release studies showed 80.7% to 83.4% after 3 hours. Even after 3 months of subjecting the tablets to 40 ºC and 75% RH, results are within acceptable range. The results show the potential of the formulation as a mucoadhesive buccal tablet.

Formulation And Characterization Of Ondansetron Hydrochloride Matrix Tablets For Sustained Drug Delivery

The objective of proposed work was to develop Ondansetron Hydrochloride (OND HCl) sustained release matrix tablets for the better treatment of vomiting for extended period of time. Sustained release matrix tablet is the drug delivery system that is designed to achieve a prolonged therapeutic effect by continuously releasing medication over an extended period of time after administration of single dose. The matrix tablets of OND HCl were prepared by direct compression method using varying ratio of hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose. The bends of tablets were evaluated for bulk and tapped density, % compressibility index and angle of repose and powder of all formulations blend exhibited that low interparticle friction and excellent flow characteristics. The prepared matrix tablets were then assessed for different physical tests like consistency of weight, thickness, hardness, friability, drug content and in vitro drug release. Each batch of the OND HCl matrix tablets were of good quality as to hardness, thickness, friability and % medicament content. The in vitro drug release study was done for 2 hours by utilizing paddle technique in 0.1N HCl (pH 1.2) as dissolution media and 6 hours using phosphate buffer (pH 6.8) as dissolution media. The drug release study showed that all formulation FMT-1, FMT-2, FMT-3, FMT-4, FMT-5 and FMT-6 were provide the drug release on sustained manner up to 8 hrs. Amongst the developed matrix tablets formulations, FMT-2 containing ethyl cellulose (100 mg) was optimized as best because FMT-2 show highest drug release profile and promoting the sustained release of drug, which could potentially improve the patient compliance.

Formulation, Development And In Vitro Evaluation Of Tramadol Extended Release Tablets

Objective: The objective of the present study was to develop “once daily” extended release tablets of tramadol (100 mg) by wet granulation using hydrophilic polymer like hydroxy propyl methyl cellulose K100M,K15M and polyethylene oxide (PEO). Methods: The tramadol matrix tablets were prepared by using different polymers like hydroxy propyl methyl cellulose (HPMC K15M and K100M), polyethylene oxide (PEO) as the nontoxic and easily available suitable matrix system. The extended release tablets of tramadol (400 mg) were prepared wet granulation technique. Different pre compression and post compression were performed. In vitro dissolution tests were performed and percentage drug release was calculated. The fourier-transform infrared spectroscopy (FTIR) studies conducted on pure drug tramadol and the optimize formulation (T6). Different release models like zero order, first order, higuchi and Korsemeyer-Peppas were applied to in vitro drug release data in order to evaluate the drug release mechanisms and kinetics. Results: Pre compression and post compression parameters satisfied with pharmacopeia specifications. The In vitro release studies were performed using USP type II apparatus showed that optimized formulation T6 consisting of polyethylene oxide (PEO) with 25 mg of the polymer was found to extended release of tramadol over a period of 24h. The optimized formulation T6 followed the zero order kinetics as correlation coefficient (r2) values are higher than that of first-order release kinetics. In order to understand the complex mechanism of drug release from the optimized formulation T6 matrix system, the in vitro release rate were fitted to Korsemeyer-Peppas model and the release exponent value (n) obtained was 0.82105 exhibited anomalous (non fickian) diffusion mechanism. Conclusion: The present study shows that polyethylene oxide was found to play a great role in controlling release of tramadol from the matrix system. Accordingly it can be concluded that the formulation is robust in the performance is less likely to be affected by the various factors studied.

Impact of Aluminum Oxide and Silica Oxide Nanocomposite on Foodborne Pathogens in Chicken Fillets

Nanotechnology is an innovative technology for improving food quality and safety. Aims: The aim of this study was to evaluate the efficacy of hydroxy propyl methyl cellulose (HPMC) films containing nanoparticles against three foodborne pathogens. Design of the Study: *This study was designed using two nanoparticles i.e. (Al2O3-NPs and SiO2-NPs), edible film (HPMC), and three foodborne pathogens i.e. Bacillus cereus, Staphylococcus aureus, and Salmonella Typhimurium. Both nanoparticles were evaluated against foodborne pathogens as well applied in chicken fillets. Place and Duration: All experiments were done in the Food Technology Department, Benha University, Egypt; Nanomaterial Laboratory, Beni-Suef University, Egypt; and Agricultural Research Center, Egypt and were done within three months. Methodology: The preparation of edible films, the antimicrobial activity, mode of antimicrobial action, challenge study, and scanning electron microscopy had been carried out in different laboratories. As well the mechanical properties of the HPMC films were evaluated. Results: The results obtained from this study showed that the nanoparticles (~80 nm) at 80 ppm were active against Bacillus cereus, Staphylococcus aureus, and Salmonella Typhimurium compared with 20 and 40 ppm. The HPMC films including Al2O3-NPs were active against B. cereus than S. aureus and S. typhimurium, while the SiO2-NPs were more effective against S. typhimurium and B. cereus compared with S. aureus. In challenge studies, HPMC films including Al2O3-NPs and SiO2-NPs at 80 ppm decreased the viability of the three-foodborne pathogens associated with chicken fillets stored at 4±1°C for 15 days, as compared with the control sample. HPMC films incorporated with nanoparticles inhibited the microbial population ~ 2-3 log10 CFU/cm2 over the chicken fillets during storage period. Conclusion: This work indicated that, HPMC films incorporated with Al2O3-NPs and SiO2-NPs (~80 nm) at 80 ppm could be reduce the microbiological loads of the refrigerated chicken fillets.

Formulation And Evaluation Of Garlic Powder Loaded Floating Matrix Tablet

Objective: The objective of the present work was to formulate and evaluate a stable, odour free garlic powder loaded floating matrix tablet for the treatment of peptic ulcers. Methods: A gastro-retentive floating matrix tablet (FMT) formulation of garlic powder (GP) was prepared using various concentrations of hydroxypropyl methylcellulose K4M (HPMC K4 M) and effervescent system (sodium bicarbonate and citric acid in 1:1 % w/w) to achieve desirable floating time (FT), floating lag time (FLT) and drug release. Wet granulation method was selected using ethanol as a binder for preparation of tablet. 32 full factorial designs were used for selection of suitable polymer concentration and effervescent system. Nonenteric film coating was applied to mask GP odour. Results: It was observed that FMT with optimum quantities of HPMC K4M and the effervescent system showed 97 % of drug release in 12 h with FT up to 10 h and minimum FLT of 3 min. There was no significant change in FLT, FT and drug content during the stability study of FMT. Conclusion: A stable, sustained release FMT of GP tablets using HPMC K4M and an effervescent system was successfully prepared. This formulation can overcome problems of taste and odour masking, gastric irritation, and loss of active constituents present in garlic.

Estimation Of Bacoside-A In Bacopa Monnieri Aerial Parts Using Tlc Densitometry

Objective: The objective of the present work was to formulate and evaluate a stable, odour free garlic powder loaded floating matrix tablet for the treatment of peptic ulcers. Methods: A gastro-retentive floating matrix tablet (FMT) formulation of garlic powder (GP) was prepared using various concentrations of hydroxypropyl methylcellulose K4M (HPMC K4 M) and effervescent system (sodium bicarbonate and citric acid in 1:1 % w/w) to achieve desirable floating time (FT), floating lag time (FLT) and drug release. Wet granulation method was selected using ethanol as a binder for preparation of tablet. 32 full factorial designs were used for selection of suitable polymer concentration and effervescent system. Nonenteric film coating was applied to mask GP odour. Results: It was observed that FMT with optimum quantities of HPMC K4M and the effervescent system showed 97 % of drug release in 12 h with FT up to 10 h and minimum FLT of 3 min. There was no significant change in FLT, FT and drug content during the stability study of FMT. Conclusion: A stable, sustained release FMT of GP tablets using HPMC K4M and an effervescent system was successfully prepared. This formulation can overcome problems of taste and odour masking, gastric irritation, and loss of active constituents present in garlic.

Formulation Design And Optimization Of Floating Matrix Tablets Of Ciprofloxacin Hcl By Using Hpmc And Ethyl Cellulose With Experimental Design

The oral floating matrix tablets of Ciprofloxacin Hydrochloride were formulated by Experimental design by using HPMC K100M and Ethyl Cellulose as the retardant polymers each with three different levels with an approach to increase gastric residence and thereby improve drug bioavailability. From FTIR results it was confirmed that there is no chemical interaction between the drug with the excipients used in tablet formulations. Also, there was no shift in the endotherm of in the drug- excipients mixtures indicating compatibility of drug with all the excipients. All the tablets were prepared by effervescent approach in which Sodium bicarbonate was added as a gas generating agent. Floating Matrix tablets were prepared by direct compression method and prepared tablets were evaluated for weight variation, percentage friability, hardness and drug content studies. All the formulations showed compliance with pharmacopeia standards (I.P. 1996). Floating lag times of all the formulations were within 1 minute and Total floating time of all the formulations were more than 12 hours. In vitro release studies revealed that the release rate decreased with increase polymer proportion of retarding polymers. The formulation CHE9 sustained release of drug for 12 hours with 21% release of drug after 1 hour and more than 97% at the end of 12 hours. From the Kinetic model it was found that the optimized formulation CHE9 showed linearity in case of Zero order (R2: 0.938) and Higuchi model (R2: 0.954). By fitting data to Korsmeyer-Peppas model and ‘n’ value lying above 0.5 indicating non Fickian release.

Study on shedding particles from Chuanping Sustained-release Tablets based on multi-marker components balanced release / 中草药

Objective: To study on the changes of shedding particles, drug loading and release of Chuanping Sustained-release Tablets (CST) which were made by the different sustained-release excipients in vitro, so as to elucidate the mechanism about balanced release of multi-marker components on Chinese materia medica compound sustained-release preparation. Methods: Using Chuanping Prescription (Ephedra Herba and Datura Flos) as model drug, improved Peach Gum and HPMC was used as sustained release materials, the release test combinied with underwater video observation were applied to shot external forms at different time point, and the laser particle sizer was applied to determinate particle size, and HPLC was applied to determine the accumulated release rate of the index components (ephedrine, pseudoephedrine, and scopolamine) to calculate the cumulative release curve slope K value, and to evaluate the balance release of the different components. Results: CST which were made by the improved peach gum and HPMC sustained-release excipient, which particles were dropped at 0.5 h after contacting the dissolution medium. At the same time, the particles were obviously shedding with the passage of time. In contrast, CST that was made by the improved peach gum, its balanced release of multi-marker components was better (K of ephedrine was 12.18, K of pseudoephedrine was 12.30, and K of scopolamine was 12.40), and particles dropped faster (it was significantly at 1 h), and particle size was bigger (D50 was 53.37—70.33 μm and D90 was 100.3—196.5 μm), and drug loading was more (ephedrine 30.63%, pseudoephedrine 32.97%, and scopolamine 31.67%), and release time of drug was longer (60—120 min). Conclusion: The shedding particles were important part of balance release of multi-marker components about CST which was made by the improved peach gum sustained-release excipient, and also was the embodiment of the drug release mode of “corrosion-dissolution”.

Effects of the critical quality attribute (cqa) of hypromellose on the release of diclofenac sodium sustained-release tablets in vitro / 中国药学杂志

OBJECTIVE: To investigate the effect of the critical quality attributes of hypromellose (HPMC) on the release profile of diclofenac sodium sustained-release tablets in vitro. METHODS: The characteristics including appearance, particle size, density, compression and specific surface area of HPMC K15M from three manufacturers (A, B and C) were studied and evaluated comprehensively. The compression data of HPMC K15M were non-linear fitted via the pressure-tensile strength curve method, Kawabe equation and Hasano equation. Sustained-release tablets were prepared by using diclofenac sodium as the active ingredient with different HPMC as gel matrix, and the in vitro release behavior of the tablets was determined in order to identify the critical quality attribute of HPMC that affect the in vitro release profile of diclofenac sodium sustained-release tablets. RESULTS: The release rate of diclofenac sodium sustained-release tablets was correlated with the substitution type of HPMC, viscosity, density and specific surface area, but less affected by particle size. CONCLUSION: Substitution, viscosity, density and specific surface area of HPMC are the CQAs factors influencing the release profile of diclofenac sodium sustained- release tablets.

Characterization of Physicochemical Properties of HPMC from Different Manufacturers and Their Effect on Sustained Release / 中国药学杂志

OBJECTIVE: To investigate the physicochemical properties of hydroxypropyl methylcellulose(HPMC)produced by different manufacturers, and to establish a link between the physicochemical properties of HPMC and its sustained release effect, which can provides a theoretical basis for further rational application. METHODS: The physicochemical properties of HPMC collected from different manufacturers, such as particle size distribution, bulk density, physical form, crystallinity and degree of substitution were characterized by laser particle size analyzer, bulk density measuring device, scanning electron microscope, X-ray diffractometer and gas chromatography, respectively. Then, the HPMC from different manufacturers were pressed into sustained release tablets, and the sustained release effect was compared by the dissolution curve. RESULTS: The physicochemical properties of HPMC produced by different factories are different, which are manifested in different particle sizes,different bulk densities, different physical shapes, whether there are differences in crystallization peaks and the content of hydroxypropoxy groups, and the different physicochemical properties directly lead to the difference of sustained release effects. CONCLUSION: The study of physicochemical properties of HPMC can better control its quality and use it more widely.

Evaluation of capsule labelling for its wall contents as gelatin or non gelatin

Background: Capsules are the most commonly used solid drug dosage form and are made up of gelatin or non gelatin. Currently the gelatin based capsules drug formulations are more used. However, current issue of vegetarian and non vegetarian capsules has come up due to recent Indian government initiative to promote vegetarian capsules.Methods: There were 100 capsule dosage forms were examined for the gelatin or HPMC wall contents and nature of medicine contained in capsules, whether ayurvedic or allopathic.Results: Out of 100 capsules studied 55 had gelatin wall base while 25 had HPMC and 20 capsule labels did not mention the nature of capsule wall constituent. Out of 55 gelatin capsules 30 were of allopathic while 25 capsules were of ayurvedic medicines. Among HPMC, 15 were ayurvedic while 10 allopathic. 20 capsules had no mention of its constituent and among these non labelled capsule formulations had 11 from ayurvedic and 9 from allopathic medicines.Conclusions: The current study revealed that gelatin capsules forms bulk in Indian market. Even the gelatin capsules contained ayurvedic medicines while 10% of HPMC capsules contained allopathic medicines. Non labelled capsules formed 20% of total capsules. These findings suggest wider scope for promotion of HPMC based capsules.

Formulation and investigation of crushed puffed rice-chitosan-HPMC based polymeric blends as carrier for sustained stomach specific drug delivery of piroxicam using 3(2) Taguchi mathematical design studies

In the present experimental investigation an attempt has been made to assess the utility of Crushed Puffed Rice (CPR)-High Molecular Weight Chitosan (HMWCH)-Hydroxypropyl Methylcellulose K15M (HPMC K15M) as a polymeric carrier for the sustained stomach delivery of Piroxicam (PRX). A total of nine formulations were prepared by using 3 (2) Taguchi factorial design, physically blending drug and polymer(s) followed by encapsulation into hard gelatin capsules size 1. The prepared capsules were evaluated for various performance such as weight variation, drug contents, in vitro buoyancy and drug release in 0.1 M HCl. The effect of drug loading on in vitro performance of the formulations was also determined. Crushed puffed rice (CPR) remained buoyant for up to average time span of 06 hr as an unwetted irregular mass in 0.1 M HCl. However, when combined with HMWCH or HPMC K15M or HPMC K15M + HMWCH a low -density cylindrical raft type hydrogel was formed which remained buoyant for up to 12 hr and released up to 99% drug in a sustained manner from 8 to 12 hr following zero order release kinetics. It was also observed that drug release from drug + CPR matrices followed Fickian mechanism. Combination of CPR + HMWCH or HMWCH + HPMC K15M also follows Fickian mechanism. Obtained data from the research work suggests that CPR in combination with HMWCH or HPMC K15M or HPMC has sufficient potential to be used as a carrier for stomach specific delivery of gastric irritant drug like PRX

Scaled-up production and application of co-processed excipient mannitol-HPMC in traditional Chinese medicine / 中国中药杂志

Spray drying technology was used to produce co-processed excipients mannitol- hydroxypropyl methylcellulose (HPMC), and study the scaled-up production. The consistency of powder and tablet properties before and after scale-up of co-processed excipients was compared, and their applicability in traditional Chinese medicine (TCM) powder's direct compression was tested on five TCM extracts such as gardenia extract and Radix Paeoniae Alba extract. It was shown that after scaled-up production, the key properties of co-processed excipients had little changes (such as compactability, disintegrating time, and lubrication sensitivity) or improvement (such as flowability and yield). As compared to commercially available spray-dried mannitol, co-processed excipients achieved better compactability and higher drug loading for direction compression of TCM powder. In conclusion, the mannitol-HPMC co-processed excipient, with excellent physicomechanical properties, is promising to be explored as a new excipient for direct powder compression.

Análise comparativa de perfis de dissolução in vitro e in silico de comprimidos de liberação modificada contendo metformina / Comparative analysis of dissolution profiles in vitro and in silico of modified release tablets containing metformin

A dissolução de um fármaco a partir de uma forma farmacêutica (FF) sólida oral é um pré-requisito para que o mesmo seja absorvido pelo organismo e cumpra seus efeitos terapêuticos. O ensaio de dissolução de medicamentos permite avaliar a quantidade de princípio ativo que é liberado a partir de sua FF, mimetizando in vitro o processo que ocorre no trato gastrointestinal (TGI). O DDDPlus® é o único programa de computador dedicado exclusivamente a simular ensaios de dissolução. O objetivo deste trabalho foi avaliar a capacidade do programa de computador DDDPlus® em fornecer perfis de dissolução in silico de comprimidos matriciais contendo metformina semelhantes aos perfis de dissolução in vitro e avaliar a possibilidade de substituir a comparação de perfis de dissolução in vitro de diferentes formulações de comprimidos matriciais contendo metformina pela comparação de perfis de dissolução in silico fornecidos pelo DDDPlus®.Para tanto, um planejamento estatístico foi realizado para obtenção de perfis de dissolução, variando a velocidade das pás e o uso do sinker. Os perfis de dissolução de 3 formulações teste (T1, T2 e T3) de comprimidos de liberação modificada por matriz polimérica contendo metformina foram comparadas pelos métodos de eficiência de dissolução (ED), tempo médio de dissolução (TMD), fator de diferença (f2) e fator de semelhança (f1). Os resultados indicaram o uso do sinker como fator determinante para a ED e TMD. Assim, o método que utilizava o sinker e a velocidade das pás de 50RPM foi utilizado para avaliar 4 produtos comercializados no Brasil. No DDDPlus® os ensaios de dissolução in vitro das formulações T1, T2 e T3 foram otimizadas para a obtenção das constantes de calibração (CC), as CC foram utilizadas para simular os ensaios de dissolução de T1, T2 e T3 em velocidades de 25 e 50RPM. Os perfis de dissolução simulados foram comparados aos perfis observados, resultando em valores de R2. Valores de R2 acima de 0,90 foram obtidos para todas as simulações realizadas utilizando CC de ensaios in vitro que utilizaram sinker, indicando o potencial do programa em auxiliar o desenvolvimento de novas formulações. Valores de R2 abaixo de 0,70 foram obtidos após a simulação de ensaios utilizando CC de ensaios in vitro que não utilizavam o sinker, indicando que o programa de computador não previu a adesão do comprimido ao fundo da cuba de dissolução durante o ensaio. Os perfis de dissolução simulados das formulações T1, T2 e T3 foram comparadas por f1 e f2 com os perfis de dissolução dos produtos do mercado. Tais comparações concluíram que o software não é indicado como substituto dos ensaios in vitro quando se almeja comparar perfis de dissolução

Dissolution of a drug from an oral solid pharmaceutical form (FF) is a prerequisite for it to be absorbed by the body and to fulfill its therapeutic effects. in vitroDrug dissolution assay allows the amount of active principle released from a FF and mimics the in vivo the process that occurs in the gastrointestinal tract (TGI). DDDPlus® is the only computer program dedicated exclusively to simulating dissolution testing. The objective of this work was to evaluate the ability of DDDPlus® software to provide in silico dissolution profiles of matrix tablets containing metformin similar to in vitro dissolution profiles and to evaluate the possibility of replacing in vitro dissolution profiles comparison of different formulations of matrix tablets containing metformin for a comparison of in silico dissolution profiles provided by DDDPlus®. For this purpose, a statistical design was used, varying agitation speed and the use of sinker to obtain dissolution profiles for 3 test formulations (T1, T2 and T3) of polymer matrix-modified release tablets containing metformin. Dissolution profiles were compared by means of dissolution efficiency (ED), mean dissolution time (TMD), difference factor (f2) and similarity factor (f1). The results indicated the use of sinker as a determinant factor for ED and TMD. Thus, the method that used sinker and agitation speed of 50RPM was used to evaluate 4 products commercialized in Brazil. in vitro dissolution tests of the T1, T2 and T3 formulations were optimized using In DDDPlus® to obtain the calibration constants (CC), which were used to simulate dissolution profiles of T1, T2 and T3 at speeds of 25 and 50RPM. in silico dissolution profiles were compared to in vitro dissolution profiles, resulting in R2 values. R2 values above 0.90 were obtained for all simulations performed using CC from in vitro assays using sinker, indicating the potential of the program to assist the development of new formulations. R2 values below 0.70 were obtained after the simulation of assays using CC from in vitro assays that did not use the sinker, indicating that the computer program did not predict adhesion of the tablet to the bottom of the dissolution cell during the assay. The simulated dissolution profiles of the T1, T2 and T3 formulations were compared by f1 and f2 with the dissolution profiles of the market products. Such comparisons concluded that the software is not indicated as a substitute for in vitro assays when comparing dissolution profiles is desired