Super Disintegrants Research Articles

Formulation, characterization, and evaluation of orodispersible tablet of a model antidepressant drug

Introduction: Paroxetine hydrochloride is used as the antidepressant drug of the selective serotonin reuptake inhibitor. It is used to treat depression resistant to other antidepressants, depression complicated by anxiety, panic disorder, obsessive-compulsive disorder (OCD). The objective of the present work is to formulate oral dispersible tablet dosage form using two different superdisintegrants.Materials and Methods: Eight formulations (F1-F8) were prepared using two superdisintegrants in varied concentrations. The optimized formulations (based on %CDR) were further formulated by sublimating agent using camphor as sublimating agent (S1, S2).Results and Discussion: All the formulated tablets were evaluated for physicochemical characteristics, drug content and in vitro drug release, dispersion time, and wetting time and the results were within the permissible limits.Conclusion: Orodispersible tablets of paroxetine HCl were successfully formulated by employing direct compression and sublimation methods. From this investigation, it can be concluded that stable orodispersible tablets gave maximum %CDR with 10% camphor as sublimating agent and 8% crospovidone as super disintegrant.

Rapimelts of Venlafaxine Hydrochloride- An Approach to Formulation and In-vitro Evaluation

The present research workwas designed to manufacture venlafaxine hydrochloride rapimelts using different super disintegrants by direct compression method. The superdisintegrants used were sodium starch glycolate Primogel croscarmellose sodium Ac-Di-Sol and crospovidone Polyplasdone XL10 in varying concentrations of 2-5. In total nine formulations of venlafaxine hydrochloride rapimelts were prepared. The preformulation studies were conducted for the prepared blends and were found satisfactory. The formulated tablets of venlafaxine hydrochloride were evaluated for parameters like friability hardness disintegration time wetting time water absorption ratio disintegration time drug content and drug release. All the evaluated parameters were found within the limits. Amongst therapimelts prepared R-IX containing 5 of crospovidone showed 100 of drug release within 20 min and was optimized as the best formulation. The rapimelts of optimized formulation was subjected for accelerated stability studies as per ICH guidelines for a period of 180 days and then evaluated for hardness wetting time water absorption ratio and in vitro dispersion time. No significant changes in the evaluated parameters indicate that the formulation was found functionally stable.

Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs.

The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.

Formulation and Evaluation of Orodispersible Tablets of Granisetron Hydrochloride Using Agar as Natural Super disintegrants

The main aim of the study was to develop orodispersible tablets of Granisetron hydrochloride a selective 5-HT3 receptor antagonist (an antivomiting agent) for improving patient compliance, especially those of paediatric and geriatric categories with difficulties in swallowing. In the wet granulation method orodispersible (ORD) tablets were prepared using natural super disintegrants Agar agar. The prepared batches of tablets were evaluated for weight variation, hardness, friability, wetting time, in vitro dispersion time, drug content and in vitro dissolution studies. The tablet formulation batch F4 was considered as the overall best formulation (with an in vitro drug release study of 99.09%). Short term stability studies (at 40 ± 2oC/75 ± 5% RH) on the best formulation indicated that there no significant changes in drug content. From the FTIR study indicated that there are no drug excipient interactions. Key words : Granisetron hydrochloride, Orodispersible tablets, FTIR spectroscopy, Wetting time, In vitro drug release study, Stability studies.

FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF GRANISETRON HYDROCHLORIDE USING PLANTAGO OVATE AS NATURAL SUPERDISINTEGRANTS

The main objective of the study was to develop orodispersible tablets of Granisetron hydrochloride, a selective 5-HT3 receptor antagonist (an antivomiting agent) for improving patient compliance, especially those of paediatric & geriatric categories with difficulties in swallowing. In the wet granulation method orodispersible (ORD) tablets were prepared using natural super disintegrants plantago ovate.The prepared batches of tablets were evaluated for weight variation, hardness, friability, wetting time, in vitro dispersion time, drug content and in vitro dissolution studies. The tablet formulation batch F4 was considered as the overall best formulation (with an in vitro drug release study of 99.11%).Short term stability studies (at 40±2oC/75±5% RH) on the best formulation indicated that there no significant changes in drug content. From the Fourier Transform Infrared (FTIR) spectroscopy study indicated that there are no drug excipient interactions. Key words : Granisetron hydrochloride, Orodispersible tablets, FTIR spectroscopy, in vitro drug release study.

Formulation and Evaluation of Meclizine Hcl Orally Dispersible Tablets by using Natural Super Disintegrants

Formulation and Evaluation of Meclizine Hcl Orally Dispersible Tablets by using Natural Super Disintegrants

Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability

The present investigation was aimed towards developing a beta-cyclodextrin (β-CD) solid dispersion (SD) based orally disintegrating tablet (ODT) of eslicarbazepine acetate (ESL), for improving the dissolution and providing fast onset of anti-epileptic action. Optimum ratio of ESL and β-CD was determined by Job's plot. Thereafter, solid dispersions were prepared by solvent evaporation method and evaluated for yield, assay, Differential scanning calorimetry (DSC), Fourier transform infra red spectroscopy (FTIR), X-ray diffraction (XRD), and in vitro dissolution. Optimized SD was compressed into ODT by direct compression using super disintegrants and evaluated for wetting time, drug content, in vitro drug release and in vivo studies. The results of DSC, FTIR and XRD analysis supported the formation of inclusion complex. An improved dissolution with 99.95±2.80% drug release in 60min was observed in comparison to 24.85±2.96% release from a plain drug suspension. Tablets with crosspovidone as a super disintegrant showed the least disintegration time of 24.66±1.52s and higher in vitro drug release against marketed tablets. In vivo studies indicated that the formulated tablets had 2 times higher bioavailability than marketed tablets. Thus, the developed β-CD–ESL SD-ODT could provide faster onset of action and higher bioavailability, which would be beneficial in case of epileptic seizures.

Formulation and evaluation of orodispersible Enalapril maleate tablets: a comparative study on natural super disintegrents and synthetic super disintegrents

The aim of the present investigation is to formulate Enalapril maleate oral disintegrating tablet by using natural and synthetic superdisintegrents..ODTs may also be used to deliver drugs to the oral cavity, for local action or, in some cases, absorption across the oral mucosa, thereby avoiding first-pass hepatic metabolism and potentially increasing the rate and extent of uptake, and reducing undesirable metabolites. The objectives of the research work is to formulate oral disintegrating tablets of Enalapril maleate by using different super disintegrates(Natural, Synthetic) in different ratio by direct compression technique and tablets were evaluated for precompressional and postcompressional Parameters such as angle of repose, bulk density, tapped density, compressibility index, drug content and in-vitro drug release study, hardness, friability, wetting time and invitro dispersion time. To study the physical characteristics of the individual drug and optimized formulations by FTIR spectroscopy. To evaluate various characteristics of the resulting tablets. Formulation CCS3, IH2 were subjected to stability Studies as per ICHguidelines at temperatures and humidity of 255C/605%RH; and 405C/755%RH.Tablets didnt reveal any appreciable changes in respect to hardness, disintegration time, drug content and dissolution profile.

Formulation and Evaluation of Mouth Dissolving Tablets of Piroxicam

Piroxicam, a non-steroidal anti-inflammatory agent, is widely used in rheumatoid arthritis, osteoarthritis, musculo-skeletal disorders, dysmenorrhoeal and post-operative pain. It has poor bioavailability due to its inherent properties. The objective of present study is to enhance water solubility of Piroxicam by solid dispersion technique and to develop novel method of preparing compressed tablets for Piroxicam with high porosity which dissolves rapidly in mouth, using camphor as sublimating agent and super disintegrants such as Crosscarmellose sodium and sodium starch glycollate. The tablets were evaluated for hardness, thickness, friability, weight variation, wetting time, disintegration time, drug content and in vitro drug release. Optimized formulation was evaluated for stability according to ICH guideline. All tablets had hardness in range of 2.8-3.1 kg/cm2 and friability of all formulations was less than 1.0%. Weight variation and drug content were within USP limits. A stability study for optimized F6 formulation 40 °C / 75 % RH for 30 days showed little change in drug content. Therefore, it is concluded that enhance solubility and increased levels of the super disintegrants Cross carmellose sodium and sodium starch glycollate increases the rate of Piroxicam release. Camphor decreases disintegration time of tablets and create high porosity which dissolve rapidly in mouth and could be industrially feasible.

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.

Development of Orodispersible Tablet of Atorvastatin Calcium Using Hot Melt Extrusion

The present study proposes to enhance solubility and eventually bioavailability of Atorvastatin Calcium (ATV) by preparing hot melt extrusion based orodispersible tablet (ODT). Tablet dosage forms displaying faster disintegration providing significant advantages over traditional techniques of solid dispersion (SD) were made by a speedy method. Dissolution analysis of the extrusion processed ATV using Soluplus in combination with Kolliphor TPGS (1:2:0.5) showed significantly increased dissolution rates and extent of supersaturation over pure drug. DSC and XRD studies revealed that ATV is converted to amorphous form during extrusion. A design of experiments (DOE) was conducted on ODT formulation to evaluate the effect of compression force and Kollidon CL-SF (super disintegrant) concentration on disintegration time, friability and hardness (p value <0.0001). The optimum formulation showed disintegration time 33±1.52 Sec, friability 0.91±0.035%, hardness 3.8±0.15 kg/cm2 and 91.18±1.2 % drug release within 15 min, thus comply US-FDA standard. The in vivo study revealed that the rate and extent of absorption of prepared tablet were higher than pure drug and marketed tablet. Cmax value of optimized formulation was 67.42±1.45 μg/ml, obviously higher than that of pure drug and marketed formulation which was 19.04±1.26 µg/ml and 56.11±1.64 µg/ml respectively. Similarly, Tmax value of former, 120 min significantly earlier compared with that of drug and marketed formulation which was 360 min and 240 min. Furthermore, Short-term accelerated stability study showed that tablets were stable at 40 °C and 75% RH as per ICH guideline. Keywords: Atorvastatin calcium, central composite design, hot melt extrusion, orodispersible tablet.

FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF DONEPEZIL HYDROCHLORIDE USING MODIFIED POLYSACCHARIDES

ABSTRACT The objective of the study was to prepare and evaluate orodispersible tablets of Donepezil Hydrochloride (DPH) using natural modified polysaccharides such as modified karaya gum and modified agar with glycine and mannitol. The prepared formulations were compared with Kyron T-314, super disintegrant, spray dried lactose, diluent for improvement in DT and other ODT parameters. FTIR studies revealed no interaction between DPH and excipients. Precompression parameters for all formulations were found to be satisfactory. The oral dispersible tablets formulated using modified agar with glycine showed better disintegration time compared to modified karaya gum formulations. Different concentrations of mannitol and glycine were used in the formulation to study the improvement in the DT. The glycine formulations with modified agar gave better ODT parameters than modified karaya gum with mannitol and glycine formulations. The optimized formulations of modified agar with glycine in different concentrations were prepared with spray dried lactose as diluent and compared with formulations of Kyron T-314 as superdisintegrant with spray dried lactose as diluent. The results of lactose and spray dried lactose as diluents in these formulations did not show any significant difference in ODT evaluation parameters. The formulations were optimized using ODT parameters such as disintegration time, wetting time, water absorption ratio and other physicochemical evaluation parameters. The accelerated stability studies of optimized formulation did not show significant changes compare to initial physicochemical evaluation parameters to conclude, modified polysaccharides with glycine can be used as superdisintegrant, which may be a cost effective alternative in comparison to synthetic superdisintegrant like Kyron T-314.

Formulation and evaluation of Nateglinide dispersible tablet by direct compression method

The study was carried to formulate and evaluate dispersible tablet dosage form obtaining Nateglinide.Nateglinideis adrugfor the treatment oftype 2 diabetes. The present study is an attempt to select best possible combination of diluents and disintegrates to formulate dispersible tablet of Nateglinide which disintegrates within few minutes thereby reducing the time of onset of action. Mannitol is selected as diluents, Sodium starch glycol ate, Cross-povidone, cross-carmellose sodium were selected as super disintegrates, citric acid and sodium bi carbonate is effervescent active ingredient in different concentrations. Aspartame as a sweetening agent, Magnesiumstearate as a Lubricant and glidant.Direct Compression method was used to formulate the tablets.All the formulations were showed the acceptable flow properties and the pre-compression parameters like Bulk density, Tapped density and Hausner ratio. The post compression parameters like Hardness, Friability, Disintegration time, Weight variation, wetting time, Dispersion time values were found to be within the IP limits.The percentage Drug content of all tablets was found to be between 99% - 100 % of Nateglinide, which is within the limit.As the concentrations of the Citric acid (preservative) &amp; sodium bicarbonate (active ingredient respectively taking increases in the formulations F7 F9 the disintegration time found to be decreased and the disintegration time for these formulations were 33, 31, 30 seconds respectively and the percentage drug release was also found to be increased for these formulations as 94 ,96, and 99 % respectively. From the above results it was found that as the concentration of citric acid decreased and sodium bi carbonate increases the disintegration and dissolution time was found to be improved, so considering the above results it was found that the F9 batch was found to be optimized batch and it pass all the pre-formulation parameters and evaluation results as per the IP limits.

Development and Evaluation of Novel Fast Disintegrating Acetaminophen Tablets

In this study, attempts were made to design and developed disintegrating drug delivery system, Acetaminophen fast disintegrating tablet (AFDT) by combining super disintegrants and direct compression method. Acetaminophen is widely used as “over the counter” and “common household drug” as analgesic and antipyretic along with poor absorption due to first pass metabolism. So we aimed to use our novel delivery system to achieve rapid absorption in patients like mentally ill, bed ridden and those who do not have easy access to water. The (AFDT) were produced by combining three super disintegrants viz. Croscarmellose, Crospovidone and Sodium starch glycolate in 4% w/w as ratio of (1:1, 1:2, 2:1) using direct compression method. The optimized batch (A3) of tablet were evaluated for post – compression parameters like hardness (4.5 ± 0.75 kg.cm2), friability ((0.76 %), wetting time (42 ± 0.92 sec), water absorption ratio (98.6 %), disintegration time (24.00 ± 0.83 sec.) were found to be acceptable according to standard limits. The in vitro release rate of acetaminophen from (AFDT) was found to be more than that simple formulation in pH (5.8) using USP dissolution test apparatus type-II. These results indicated that, the new (AFDT) formulation system combined advantage of faster release of acetaminophen, which had better effects of rapid oral absorption. Therefore, the AFDT may be used as fast disintegrating delivery system for OTC drug with poor absorption due to first pass metabolism.

Formulation and Evaluation of Fast Dissolving Tablets of Cefixime Trihydrate

Fast Dissolving Tablet instead of dissolving or disintegrating in water is expected to dissolve or disintegrate in oral cavity without drinking water. Super disintegrates are added to a drug formulation to facilitate the break-up or disintegration of tablet or capsule content into smaller particles that can dissolve more rapidly than in the absence of disintegrates In the present study, the effects of a natural superdisintegrants Plantago ovata, Hibiscus rosa sinensis and synthetic superdisintegrants like sodium starch glycolate (SSG), Crosspovidone and Croscarmellose sodium (Ac-di-sol) were compared in the formulations of fast dissolving tablets (FDT). FDTs of Cefixime were prepared by direct compression method and were evaluated for weight variation, hardness, thickness, disintegration time, wetting time, water absorption ratio, In vitro dispersion, friability and dissolution. Among all the super disintegrates, Plantago ovata showed the highest swelling index and natural super disintegrates like husk of Plantago ovata showed better disintegrating property than the most widely used synthetic super disintegrates like AC-di-Sol, C.P and SSG in the formulations.

In vitro and in vivo evaluation of fast-dissolving tablets containing solid dispersion of lamotrigine.

Aim:Investigation of in vitro/in vivo behavior of fast-dissolving tablets containing solid dispersions (SDs) of lamotrigine (LM) was the aim and focus of the present research work.Material and Methods:The effect of various hydrophilic polymers on the aqueous solubility of LM was studied. Polyethylene glycol (PEG 6000) was selected as the vehicle and SDs were prepared by melting and solvent evaporation method (SEM). Evaluation of SD for dissolution indicated SVM was more appropriate as seen from an enhancement in drug dissolution. Infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction studies indicated a lack of physicochemical interaction between the drug and the carrier. A total of nine formulations were compressed into fast-dissolving tablets using Avicel pH 102 as a directly compressible filler and ac-di-sol, sodium starch glycolate and crospovidone as super disintegrates and evaluated for pre- and post-compression parameters and in vitro drug release.Results:Mathematical analysis of in vitro data suggested that first order was most suitable mathematical model for describing the optimized formulation. Stability studies indicated that the effect of storage was insignificant at 5% level of confidence. In vivo studies of pure drug, selected formulation and marketed product were carried out in male Wistar rats and pharmacokinetic (PK) parameters were calculated using PK function for Microsoft Excel. The best formulation has shown Tmax of 0.5 h which was highly significant (P < 0.05) when compared with pure drug and marketed formulation. The statistical significance was assessed by one way analysis of variance.Conclusion:Therefore, the SDs prepared by SEM using PEG 6000 as hydrophilic carrier can be successfully used for improvement of dissolution of LM and resulted in faster onset of action as indicated by in vivo studies.

Design, Development and Evaluation of Solifenacin Succinate Tablets

Solifenacin Succinate is used in the treatment of over active bladder with symptoms of urge urinary incontinence, urgency, and increased urinary frequency, and anti spasmodic. Solifenacin Succinate was launched in 2005 and has been shown in both short and long term clinical trials to fulfill these requirements. Solifenacin is a competitive M3 receptor antagonist with a long half-life (45–68 hours). It is available in two dosage strengths namely a 5 or 10 mg once-daily tablet. Ten different trial batches were carried out using different concentrations of excipients like binder (Methocel E5 premium LV), super disintegrant (sodium starch glycolate, cross carmellose sodium, cross povidone), lubricant (Magnesium stearate), glidant (Aerosil) by direct compression technique. The pre-compression parameters and post compression parameters of Solifenacin Succinate tablets were evaluated. The tablets were evaluated for in-vitro drug release studies. Based on similarity factor f2 cross povidone (1.17%), Methocel E5 premium LV (3%), Magnesium starate (1.47%), Aerosil (0.529%) was selected.

Formulation Development and Evaluation of Mouth Dissolving Tablet of Anti-allergic Drug (Astemizole)

Mouth dissolving tablets are those that dissolve or disintegrate quickly in the oral cavity, resulting in solution or suspension. In the present study Mouth dissolving tablet of Astemizole was prepared by direct compression method using crosspovidone, Crosscarmellose and Indion 414, as superdisintegrants. Tablet was formulated by using different super disintegrants such as Crosscarmellose, Crosspovidone and Indion 414 in the ratio of 6%, 9% and 12% as represented by F1 to F9 respectively. The tablets prepared were evaluated for various parameters like various density parameters, thickness, hardness, friability, disintegration time, wetting time and In-vitro dissolution time. All the parameters were found to be within limits. The developed formulation of Astemizole batch F8 (9% Indion 414) showed good palatability and dispersed within 30 seconds as compared to crosscarmellose. In vitro dissolution study of Different Formulation with 9% crosscarmellose sodium, crosspovidone and Indion 414 showed maximum dissolution rates with 81.32%, 85.3% and 95.48% respectively of the drug released in 4 minutes. The best fitted model for the optimized formulation of F8 batch was found to be higuchi model. Higuchi model show the maximum release of drug having R value 0.996.

Development and Evaluation of Bilayer Tablet of Metoclopramide HCl and Aceclofenac

Bilayer tablets are basically used to administer a dosage form with dual release effect or to formulate two incompatible drugs. The main objective of the present research work was to prepare bilayer tablet of Metoclopramide hydrochloride (MTH) and Aceclofenac (ASF) for separate layers to avoid the degradation of the drug, with the desired release pattern and thus to maximize the efficacy of both drugs in combination for the effective treatment of migraine. MTH and ACF were formulated as immediate and conventional release layer respectively. ASF was formulated as conventional release layer using PVP K-30 and MCC as binder and disintegrants respectively. MTH was formulated as immediate release layer by using various disintegrants like Sodium starch glycolate (SSG), Cross carmellose sodium (CCS) and Pre-gelatinized starch (PGS). Mixture design technique was used to find out the optimized quantity of the super disintegrants. Disintegration time (DT) and drug release at 15 min (Rel15min) were taken as dependent variables while quantity of super disintegrants was taken as independent variable. SSG and CCS in a concentration of 7.5% and 4.5% respectively gave a DT of 9 sec, and 98.67% release at 15 min (Rel15min). Stability studies of bilayer tablets as well as physical mixture were carried out and the samples were evaluated with DSC, FT-IR and % content of drug. Bi-layer tablet was suitable for preventing direct contact of these two drugs and thus to maximize the efficacy of combination of two drugs for migraine.

Study on the Effect of HPMC on Compression Coated Floating Pulsatile Delivery of Bisoprolol

The present work aimed to develop and study the effect of HPMC on compression-coated floating - pulsatile delivery of Bisoprolol. Inner core tablet contains bisoprolol and a super disintegrant. Outer shell contains HPMC K4M and HPMC K100M as erodible layer along with a gas generating agent. Compression-coated tablet of bisoprolol with 120mg HPMC K4M (B2) showed a lag time of 3.40±0.1 hrs with 99.81% drug release. Whereas 110mg HPMC K100M (B5) showed a lag period 4.0±0.1 hrs with 98.91% drug release. A 32 factorial design was applied. HPMC K4M CR and K100M were independent variables whereas drug release, lag time at 4 hrs and swelling index were dependent variables. To understand the interaction of independent variables on dependent variables three dimensional surface response plots were drawn. The responses exhibited by batch F4 (55 mg HPMC K4M and 65 mg K100M) showed lag time 4.20 hrs following the sigmoidal release pattern. Optimized batch F4 gave good in-vitro in -vivo correlation. Keywords: Bisoprolol, compression, floating tablet, HPMC, lag time, pulsatile drug delivery system.