Superdisintegrants Sodium Starch Glycolate Research Articles

Development and Evaluation of an Orodispersible Tablet Formation for the Delivery of a Hydrophobic Drug.

Orodispersible tablet (ODT) is a promising avenue for drug delivery, offering a dosage form that can be disintegrated instantaneously in the mouth and released the drug that dissolves or disperses in the saliva without the addition of water. ODT can effectively boost the dissolution rate and consequently the bioavailability of several hydrophobic drugs. Additionally, ODT is very attractive and suitable for specific patients who are unable to swallow the traditional tablet. The basic approach in the fabrication of oral tablets for hydrophobic drugs relies on the utilization of superdisintegrants which allow prompt disintegration of tablets after swallowing. In the present investigation, escitalopram oxalate was chosen as a model drug, which is a hydrophobic, antidepressant, selective serotonin reuptake inhibitor (SSRI) drug. Nine formulas of escitalopram oxalate ODTs were prepared by varying the concentrations of three different superdisintegrants: sodium starch glycolate, croscarmellose sodium, and crospovidone to improve the dissolution and release of escitalopram oxalate. Each was used in three different concentrations (2.5%, 5%, and 7.5%), and all the ODTs were prepared by the direct compression method. The micrometric characterization of the powder blend used in the formulations was investigated such as angle of repose, bulk and tapped densities, compressibility percent (Carr's index), and Hausner ratio. Furthermore, the prepared ODTs were characterized in terms of weight variation, thickness, diameter, hardness, friability, in vitro disintegration, wetting time, water absorption ratio, drug content, in vitro dissolution, and accelerated stability study. The results showed that the formula (ODT9) that contained 7.5% of the superdisintegrant sodium starch glycolate had superior characteristics in almost all the tests, with a dissolution rate of 100% after 6 minutes. Also, it was stable under the accelerated stability conditions.

Formulation and characterization of metformin hydrochloride orodispersible tablets with super disintegrants

Metformin hydrochloride's fast onset of action is very desirable, making it a prime candidate for the preparation of orodispersible tablets in the present study. This medication is prescribed for the management of type 2 diabetes, which does not respond to insulin. The tablets were made using direct compression and a mixture of the super disintegrants sodium starch glycolate (SSG) and croscarmellose sodium (CCS). Mannitol is a sugar-based excipient that serves as a binding agent, dissolves well in water, and provides a pleasant mouth feel. The blend's pre-compression results show that the medication excipients work well together and have desirable compression characteristics. Eight distinct formulations with varying amounts of SSG, CCS, and Mannitol were made. The properties of the tablets' drug release were measured, including their in vitro disintegration time, water absorption ratio, mechanical stability, wetting time, and so on. When using a greater concentration of SSG, CCS, and Mannitol, formulations F4 and F8 showed shorter in vitro disintegration times of 10.2 and 7.8 ​s, respectively, and formulation F8 showed 99.65% in vitro drug release at the end of 30 ​min. The orodispersible tablet performance can be enhanced through direct compression using the super disintegrants inclusion methodology.

Development and Evaluation of Floating Sustained Release Bilayer Tablets Containing Dothiepin HCl

Bilayer floating tablets of Dothiepin HCL were developed by direct compression method. Immediate release layer contains 30 mg of drug and super disintegrant sodium starch glycolate, serves the purpose of loading dose. Sustained release layer contained HPMC K4M, natural polymers like xanthan gum, guar gum, karaya gum release the drug for 12 hours’ time. Sodium bicarbonate and citric acid are used to produce effervescence. Floating lag time of optimized tablet is 92 sec, whereas floating duration is more than 12 hours. FTIR results revealed that there was no interaction between drug and HPMC K4M / xanthan gum. The post compression parameters of developed tablets were found to be satisfactory. In this study, it was confirmed that the formulations containing HPMC K4M, have shown better floating properties and finally the formulation containing a combination of HPMC K4M and xanthan gum in 3:1 ratio, has exhibited decent sustained drug release properties. The release kinetics of optimized formulation prepared with the combination of HPMC K4M and xanthan gum followed zero order kinetics. Keywords: Floating Bilayer Tablet, Dothiepin HCL, HPMC K4M, Xanthan Gum, FTIR.

Influence of Various Disintegrants on the Quality of Microcrystalline Cellulose Tablets

The effects of the superdisintegrants sodium starch glycolate, croscarmellose sodium, polacrilin potassium Kyron T-314, and Amberlite IRP 88 on the quality parameters of placebo tablets prepared from microcrystalline cellulose were studied. Sodium starch glycolate was most effective with croscarmellose sodium and Amberlite IRP 88 slightly less. All studied disintegrants gave dosage forms of pharmacopoeial quality. The effects of disintegrant concentration and particle type on tablet hardness were determined. The dosage form hardness increased with increasing disintegrant content for croscarmellose sodium with fibrous particles and decreased for sodium starch glycolate and polacrilin potassium with round and irregularly shaped particles. The tablets were harder if polacrilin potassium was added to the formulation.

CALCIUM SALT OF CARBOXYMETHYLED AEGLE MARMELOS (BAEL FRUIT) GUM: A NOVEL SUPERDISINTEGRANT FOR FAST DISINTEGRATING TABLETS.

The present study was carried out for the preparation of modified Aegle marmelos gum as natural superdisintegrant and assessed it on various parameters for preparing fast dissolving dosage form. The extracted gum from Aegle marmelos fruit is chemically modified by carrying out its carboxymethylation and further complexed with Calcium chloride. Therefore, the natural Superdisintegrant prepared from Aegle marmelos gum followed swelling and wetting mechanism for disintegration of the dosage form. The change in the functional groups of the extracted gum, carboxymethyled gum and the calcium complexed gum was studied by FT-IR spectrophotometer and DSC studies. Pre-compression parameters of the tablet such as Swelling index, bulk density, tapped density, carr’s index, angle of repose and hausner’s ratio were determined. Dummy tablets containing calcium complexed Aegle marmelos gum were formulated to check the disintegrating efficiency of the tablets. The disintegrating properties of calcium complexed Aegle marmelos gum as superdisintegrant was compared with the marketed Superdisintegrant Sodium starch glycolate. The comparison between both the formulations containing different superdisintegrants in various batches was done to check the disintegrating efficiency of the modified Aegle marmelos gum as superdisintegrant. The disintegrating time for calcium complexed Aegle marmelos gum was observed to be 1min±2sec to 1min±5sec showing good disintegrating properties.The present study may serve as a prototype approach for formulation and development of novel superdisintegrant from various natural gums.

DEVELOPMENT OF BILAYER TABLETS FOR IMMEDIATE AND CONTROLLED RELEASE OF ALLICIN

Objective: The purpose of this study was to develop and evaluate bilayer tablet for the immediate and controlled release of Allicin (Garlic Extract) for effective treatment of Hypertension.Methods: The immediate release layer was prepared by using super disintegrants-sodium starch glycolate and binder used xantham gum and the sustained release layer was prepared by using hydrophilic polymer like HPMC K 100 and PVP. Before preparation of the tablets, all the pre-formulation parameters were checked and the tablet of Allicin were prepared by direct compression method and was evaluated for physical characteristics like hardness, weight variation, drug content and friability. In vitro release of drug was performed USP type II dissolution test apparatus using phosphate buffer (pH 7.4) as dissolution media and dissolution was continued for 8 hrs for the sustained release layer.Results: It was found that all the formulations were within the limit of the standard. The drug release of the tablet was in the range of 66%-83% in 8 h.Conclusion: It was concluded that the F4 formulation showed the optimum result as a bilayer tablet for the effective treatment of hypertension.

Formulation and Evaluation of Modified Pulsincap as Pulsatile Drug Delivery System for Treatment of Rheumatoid Arthritis

The aim of the present study was to design and evaluate a modified pulsincap pulsatile drug delivery system of etodolac for treatment of rheumatoid arthritis. Capsule body was made water insoluble by cross linking with formaldehyde vapour. It was filled with drug, osmogen NaCl and super disintegrant sodium starch glycolate to expel the drug after predetermined lag time. A hydro gel plug made of HPMC K4M was placed in the capsule body to achieve desired drug release after lag time for chronotherapy of rheumatoid arthritis. Untreated cap was then fitted to the treated body was sealed. Entire unit was coated with 5% Eudragit S-100 to prevent variable gastric emptying. A 32 full factorial design was used for optimization in which concentration ratio of NaCl and SSG (X1), and the weight of hydrogel plug (X2) were selected as independent variables while lag time and t90% were taken as dependent variables. FTIR and DSC studies confirmed drug excipient compatibility. Developed formulation was evaluated for in-vitro drug release in pH 1.2, phosphate buffer pH 6.8 and phosphate buffer pH 7.4. Statistical analysis confirmed the significance of selected independent variables. Response surface plot and contour plot indicate augmentation of the line toward the weight of hydrogel plug factor indicating greater significance. Formulation with highest desirability containing 34.4 mg of SSG, 137.6 mg of NaCl and 48 mg of HPMC K4M plug was selected as an optimized formulation as it provided the desired lag time of 6 hours and t90% of about 477 mins. Accelerated stability study performed on optimized formulation suggested stable and viable formulation. A stable, efficient formulation modified pulsincap of Etodolac as a pulsatile drug delivery system was developed with proposed increased patient compliance and improved dosage form efficiency.

FORMULATION AND OPTIMIZATION OF CEFIXIME TRIHYDRATE DISPERSIBLE TABLETS BY DIRECT COMPRESSION TECHNIQUE

The optimized formulation of cefixime dispersible tablets were developed using super disintegrants sodium starch glycolate and crospovidone. D-optimal design is used to optimize the formulation of cefixime dispersible tablet to study the effective concentration of independent variables SSG, crospovidone and MCC on responses (dependent variables) i.e. dispersion time, % drug release and % friability. Twelve formulations were prepared and evaluation of pre-compression and post compression parameters of tablets was perfomed. Analysis of variance (ANOVA) probability (p) < 0.05 for responses was found to be significant. A response surface plot is also presented graphically to represent the effect of the independent variables on the dispersion time, % friability and % drug release. Finally, a checkpoint batch is prepared to prove the validity of evolved method. The stability studies of the optimized formulation F13 were carried as per ICH guidelines proved that the optimized formulation was stable even after 2 months.

Design of Gastroretentive Floating Bilayer Tablets of Metformin and Glimepiride

The present study involves designing and development of a bilayer tablet of Metformin HCl (MET) and Glimepiride (GLP) to offer immediate release of GLP and gastroretentive layer of MET. Bilayer tablets containing two layers i.e. immediate release layer formulated using super disintegrant Sodium starch glycolate and gastroretentive layer formulated with polymers like HPMC K4M and HPMC K100M to modulate the biphasic drug release. Wet granulation method was employed to formulate bilayer tablets. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM) were used for physicochemical compatibility and stability studies of the tablets. Accelerated stability studies were followed in compliance with ICH guidelines. The in vitro release profile shows desired biphasic release behavior after storage at accelerated condition (40°C± 2°C and 75%RH ± 5% RH) for 6 months. Biphasic drug release pattern was successfully achieved through the formulation of bilayer tablets that are stable and capable of releasing the drug over 12 hrs.

Comparative binding and disintegrating property of Echinochloa colona starch (difra starch) against maize, sorghum, and cassava starch

Context: Starch obtained from different botanical sources exhibit different characteristics due to variation in amylase–amylopectin ratio, which results in different binder substrate interactions.Objective: The present study characterized Echinochloa colona (L.) Link (Poaceae) starch and evaluated its compressional characteristics for use as tablet excipient against commonly used maize, sorghum, and cassava starch.Materials and methods: Three experimental design studies were performed to determine the effects of the maize starch and povidone on physical properties of paracetamol (250 mg) tablets. The effect of superdisintegrants sodium starch glycolate and croscarmellose sodium on the optimized composition obtained in the preceding experiments was evaluated in two factorial experimental studies. The maize starch in the optimum formulations was replaced with difra, sorghum, and cassava starch, and tablets prepared from these starches were compared for their compressional characteristics, lubrication sensitivity, moisture uptake, and drug release.Results: Tablets prepared from maize starch and povidone (30:9, w/w) blend which was previously mixed for 8 min disintegrated (DT) in 10 min. Superdisintegrants decreased DT of tablets significantly (p < 0.05) to 2.2 min. The Hausner ratios of co-processed mixtures containing sorghum, maize, and difra starch were 1.19, 1.21, and 1.26, respectively, with equilibrium moisture content of 8–9%. The DT of sorghum and difra starch formulations which related directly to their higher hydration capacity (difra > sorghum > maize starch) and swelling property was 1.5 min and 2.5 min, respectively, with a friability of 0.32%. The effect of lubrication on the DT and friability of tablets containing maize and difra starch was significant (p < 0.05). However, more than 90% drug was released in vitro dissolution studies.Conclusion: Difra starch can replace maize and sorghum starch as tablet excipient.

Effect of synthetic super disintegrants and natural polymers in the preparation of donepezil hydrochloride fast disintegration films

The main aim of the present research was to develop a fast dissolving oral polymeric film with good mechanical properties, faster disintegration and dissolution when placed on tongue. Donepezil hydrochloride (DPH) is prescribed in the treatment of mild to moderate Alzheimer’s disease (AD). The polymers selected for preparing films were sodium alginate (SA), poly vinyl alcohol (PVA) and guar gum (GG). Three batches of films were prepared by solvent casting method with sodium alginate, sodium alginate &amp; PVA and with the combination of sodium alginate &amp; guar gum. From these three batches, three optimized film formulations S3, SP7 and SG8 were selected based on disintegration time. To these three selected film formulations, superdisintegrants sodium starch glycolate (SSG), cross carmellose sodium (CCS) and cross povidone (CP) were added at a concentration of 4% w/w of polymer to improve the disintegration time. The films prepared with or without superdisintegrants were compared for fast releasing properties. Based on DT and in vitro dissolution data, S3CP was selected as the best formulation among the all formulations.DOI: http://dx.doi.org/10.3329/icpj.v3i3.17892 International Current Pharmaceutical Journal, February 2014, 3(3): 243-246

Development of Directly Compressible Mucoadehsive Fast Disintegrating Sublingual Tablet System of Piroxicam Using 3 factor, 3 Level Box Behnken Design

Piroxicam is a non steroidal anti-inflammatory drug with analgesic properties. The purpose of this study was to develop a mucoadhesive fast disintegrating tablet of poorly soluble Piroxicam by direct compression technique using superdisintegrant sodium starch glycolate and interactive mixture was characterized by physicochemical parameters. A Box Behnken design was applied to systematically optimize the drug disintegration time. Independent variables studied were the amount of Disintegrant (X1), amount of Bioadhesive (X2) and amount of Binder (X3). The dependent variables were Hardness (Kg/cm2) (Y1), Disintegration time (sec), (Y2) friability (%) (Y3) and wetting time (sec) (Y4). The prepared tablets were evaluated physical properties hardness, friability, disintegration time, wetting time and In-vitro drug release.

FORMULATION AND EVALUATION OF METOCLOPRAMIDE RAPIDLY DISINTEGRATING TABLETS

Metoclopramide an effective antiemetic; acting on the CTZ, blocks apomorphine induced vomiting. Rapidly disintegrating tablets of metoclopramide hydrochloride were prepared by mass extrusion technique using three different superdisintegrants Sodium Starch Glycolate, Avicel Ph 102, L-HPC. Pre-compression parameters and post-compression parameters were evaluated for all the nine formulations. Angle of repose and % compressibility showed good flowability in all the formulations. Weight variation was found within limits and drug content of all the formulations was found in the range of 9.700 mg - 9.925 mg in each tablet. The hardness of all the formulations was almost uniform and possessed good mechanical strength with sufficient hardness. The wetting time in all the formulation was fast. Formulations F3 containing sodium starch glycolate 10% &amp; F6 containing Avicel ph 102 10% tablets disintegrated rapidly to release the drug. In vitro release studies revealed that 96% of drug releases from SSG, MCC (90%), and L-HPC (85%) for all the formulations were within 15 min. Based on above results, three formulations F3, F6, F9 were selected for stability studies these formulations showed not much variation in any parameter even after the period of 30 days, formulations F3, F6, F9 are found to be stable and retained their original properties. Thus, it may be concluded that formulation containing sodium starch glycolate as superdisintegrants is fulfilling all the parameters satisfactorily. It showed excellent in vitro disintegration, in vitro dispersion time, compared to other superdisintegrants. And the rapidly disintegrating tablets can be prepared by mass extrusion technique Â

Design, development and in vitro-in vivo study of a colon-specific fast disintegrating tablet

Objective: Targeted delivery systems for the treatment of Inflammatory bowel disease (IBD) are designed to increase local tissue concentrations of anti-inflammatory drugs from lower doses compared with systemic administration. The objective of this study was to formulate and evaluate an oral system designed to achieve site-specific and instant drug release in the colon for effective treatment of IBD.Materials and methods: The system consists of a core tablet containing the model drug diclofenac sodium, superdisintegrant sodium starch glycolate, and coated with enteric polymer Eudragit FS 30 D to achieve different total percentage weight gain. Drug release studies were carried out using a changing pH method. A placebo formulation containing barium sulphate in the tablet was administered to human volunteers for in vivo X-ray studies. SEM studies were performed to determine coating thickness and film topography.Results: In vitro studies revealed that the tablet with 10% coating level released the drug after 5 h lag time corresponding to the colonic region. Tablets with 10% coating level could maintain their integrity in human volunteers for 5 h, approximating colon arrival time and release the drug instantaneously.Discussion: Colon-targeting and instant drug release for 10% coating level was due to the dissolution of the Eudragit FS 30 D and the immediate release effect of superdisintegrant. It was observed that as the coating level increased, the lag time also increased. This was because of increased diffusion path length and tortuosity at higher coating levels.Conclusion: An in vivo-in vitro study revealed that not only the sensitivity of the polymer to the pH environment but also the thickness of coating plays an important role in colon delivery and the tablet with 5% superdisintegrant and 10% coating level achieved the desired performance of the colon targeting.

Physicochemical and Pharmaceutical Properties of Cross‐Linked Carboxymethyl Rice Starch Prepared by a Simultaneous Dual Reaction

ABSTRACTCross‐linked carboxymethyl rice starches (CL‐CMRS) were prepared from reactions between a native Klong Luang 1 (KL1) rice starch and varied concentrations (2.5–15% w/w) of sodium trimetaphosphate (STMP) in simultaneous carboxymethylation and cross‐linking reactions set up using methanol as a solvent. Physicochemical as well as pharmaceutical properties of CL‐CMRS were evaluated in relation to the amount of STMP used and the degree of cross‐linking (DCx). At a low DCx, the viscosity of CMRS solution was enhanced through the formation of cross‐linked polymeric network and chain entanglement. At higher concentrations in the preparation reaction, STMP caused proportional decreases in the water solubility and ≤70‐fold of the solution viscosity, but promoted swelling and water uptake of the modified starches. Rheological behavior of the nonsoluble but swellable CL‐CMRS was similar to that of commercial superdisintegrants sodium starch glycolate (SSG), and cross‐carmellose sodium (CCS). The swelling and water uptake of CL‐CMRS were 5–7 and 6–25 times higher, respectively, than that of the native starch. Disintegration test of tablets containing 1 and 3% w/w of native and modified rice starches showed that M‐KL1‐5 and M‐KL1‐10 could be developed as tablet disintegrants.

Formulation design and optimization of tastemasked mouth-dissolving tablets of Tramadol hydrochloride

The aim of the present study was to mask the extremely bitter taste of Tramadol HCL, an opioid analgesic, and to formulate a tablet which can rapidly disintegrate in saliva (rapidly disintegrating tablet). The crucial aspect in the formulation of mouth-dissolving tablets is to mask the bitter taste and to minimize the disintegration time. Taste masking was done using sweetening agent and D-mannitol and taste-masked pellets were prepared by extrusion spheronization technique. Prepared pellets were tested for drug content, taste evaluation in oral cavity and molecular property. Pellet shows significant taste masking, confirmed by in vitro taste evaluation; therefore, it was selected for further study. Pellets were evaluated for density, angle of repose, Carr’s index, Hausner’s ratio and sphericity while tablets were evaluated for disintegration and in vitro dissolution. A 32 full factorial design and statistical models were applied to optimize the effect of two factors, i.e. superdisintegrant sodium starch glycolate and taste-masking agent (D-mannitol). In this study, response surface methodology was used for designing of the experiment, generation of mathematical models and optimization study. Taste evaluation of pellets in human volunteers revealed considerable taste masking with a degree of bitterness below threshold value (2.0) within 10 s, whereas Tramadol HCl was rated intensely bitter with a score of +4 for 10 s. The size of the pellets varied from 0.895 to 1.423 mm for different batch and found to be a spherical. Disintegration time of different formulations varied from 30 to 60 s. It was observed that the responses, i.e. disintegration time and sphericity were affected by both the factors. The statistical models were validated and can be successfully used to prepare optimized taste-masked mouth-dissolving tablets of Tramadol HCl with adequate disintegration and shape. Key words: 32 factorial design, rapidly disintegrating tablet, response surface methodology, taste-masked granule, Tramadol HCL

Design and evaluation of sustained release bilayer tablets of propranolol hydrochloride

The objective of the present research was to develop a bilayer tablet of propranolol hydrochloride using superdisintegrant sodium starch glycolate for the fast release layer and water immiscible polymers such as ethylcellulose, Eudragit RLPO and Eudragit RSPO for the sustaining layer. In vitro dissolution studies were carried out in a USP 24 apparatus I. The formulations gave an initial burst effect to provide the loading dose of the drug followed by sustained release for 12 h from the sustaining layer of matrix embedded tablets. In vitro dissolution kinetics followed the Higuchi model via a non-Fickian diffusion controlled release mechanism after the initial burst release. FT-IR studies revealed that there was no interaction between the drug and polymers used in the study. Statistical analysis (ANOVA) showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05) in the amount of drug released after 12 h from optimized formulations was observed.

Improvement of dissolution of poorly soluble drugs by solid deposition on a super disintegrant. II. The choice of super disintegrants and effect of granulation

It is demonstrated that the dissolution from capsules and tablets of poorly soluble, hydrophobic drugs can be strongly improved by solid deposition of the drug upon hydrophilic, strongly swelling carriers like the super disintegrants sodium starch glycolate and croscarmellose sodium. As an effect of its lower swelling power, the super disintegrant crospovidone is far less effective than the other super disintegrants. Wet granulation of poorly soluble drugs with high concentrations of sodium starch glycolate resulted likewise in a strongly improved drug release and bioavailability from capsules and tablets. It was found, however, that granules containing a too high concentration of the super disintegrant slow down the drug release from tablets. This effect is caused by the formation of a viscous barrier of the super disintegrant in the granules during the dissolution process.