Formulation design and optimization of fast dissolving clonazepam tablets by sublimation method.

Fast dissolving tablets of clonazepam were prepared by sublimation method with a view to enhance patient compliance. A 3(2) full factorial design was applied to investigate the combined effect of two formulation variables: amount of croscarmellose sodium and camphor. Croscarmellose sodium (2-8% w/w) was used as superdisintegrant and camphor (20-40% w/w) was used as subliming agent, to increase the porosity of the tablets, since it helps water to penetrate into the tablets, along with directly compressible mannitol to enhance mouth feel. The tablets were evaluated for hardness, friability, thickness, drug content uniformity, in vitro dispersion time, wetting time and water absorption ratio. Based on in vitro dispersion time (approximately 11 s); the formulation containing 5% w/w croscarmellose sodium and 40% w/w camphor was found to be promising and tested for in vitro drug release pattern (in pH 6.8 phosphate buffer). Short-term stability (at 40°/75% relative humidity for 3 mo) and drug-excipient interaction. Surface response plots are presented to graphically represent the effect of independent variables on the in vitro dispersion time. The validity of the generated mathematical model was tested by preparing two extra-design checkpoints. The optimized tablet formulation was compared with conventional commercial tablet formulation for drug release profiles. This formulation showed nearly nine-fold faster drug release (t(50%) 1.8 min) compared to the conventional commercial tablet formulation (t(50%) 16.4 min). Short-term stability studies on the formulation indicated that there are no significant changes in drug content and in vitro dispersion time (P<0.05).

Formulation design of fast disintegrating tablets using disintegrant blends.

In the present work, fast disintegrating tablets of prochlorperazine maleate were designed with a view to enhance patient compliance by direct compression method. In this method, crospovidone (up to 3% w/w) and croscarmellose sodium (up to 5% w/w) in combination were used as superdisintegrants. Since disintegrants complement each other, accelerating the disintegration process when used together. Estimation of prochlorperazine maleate in the prepared tablet formulations was carried out by extracting the drug with methanol and measuring the absorbance at 254.5nm. The prepared formulations were further evaluated for hardness, friability, drug content uniformity, in vitro dispersion time, wetting time and water absorption ratio. Based on in vitro dispersion time (approximately 12 s), one promising formulation was tested for in vitro drug release pattern in phosphate buffer pH 6.8 and short-term stability (at 40 degrees /70% RH for 3 mo), drug-excipient interaction (IR spectroscopy) were studied. Among the formulations tested, formulation DCPC(4) containing 5% w/w of croscarmellose sodium and 3% w/w of crospovidone as superdisintegrant emerged as the overall best (t(50%) 7.0 min) based on drug release characteristics in pH 6.8 phosphate buffer compared to commercial conventional tablet formulation (t(50%) 17.4 min). Short-term stability studies on the promising formulation indicated that there were no significant changes in drug content and in vitro dispersion time (p<0.05).

Formulation design and optimization of fast disintegrating Lorazepam tablets by effervescent method.

Fast disintegrating tablets of lorazepam were prepared by effervescent method with a view to enhance patient compliance. A 3(2) full factorial design was applied to investigate the combined effect of two formulation variables: amount of crospovidone and mixture of sodium bicarbonate, citric acid and tartaric acid (effervescent material) on in vitro dispersion time. Crospovidone (2-8% w/w) was used as superdisintegrant and mixture of sodium bicarbonate, citric acid and tartaric acid (6-18% w/w) was used as effervescent material, along with directly compressible mannitol to enhance mouth feel. The tablets were evaluated for hardness, friability, thickness, drug content uniformity and in vitro dispersion time. Based on in vitro dispersion time (approximately 13 s); the formulation containing 8% w/w crospovidone and 18% w/w mixture of sodium bicarbonate, citric acid and tartaric acid was found to be promising and tested for in vitro drug release pattern (in pH 6.8 phosphate buffer), short-term stability and drug-excipient interaction. Surface response plots are presented to graphically represent the effect of independent variables (concentrations of crospovidone and effervescent material) on the in vitro dispersion time. The validity of the generated mathematical model was tested by preparing two extra-design check point formulations. The optimized tablet formulation was compared with conventional marketed tablet for drug release profiles. This formulation showed nearly eleven-fold faster drug release (t(50%) 2.8 min) compared to the conventional commercial tablet formulation (t(50%) >30 min). Short-term stability studies on the formulation indicated that there were no significant changes in drug content and in vitro dispersion time (P<0.05).

Plantago ovata Mucilage in the Design of Fast Disintegrating Tablets.

In the present work, fast disintegrating tablets of prochlorperazine maleate were designed with a view to enhance patient compliance by direct compression method. In this method mucilage of Plantago ovata and crospovidone were used as superdisintegrants (2-8% w/w) along with microcrystalline cellulose (20-60% w/w) and directly compressible mannitol (Pearlitol SD 200) to enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity, wetting time, water absorption ratio and in vitro dispersion time. Based on in vitro dispersion time (approximately 8 s), the two formulations were tested for the in vitro drug release pattern (in pH 6.8 phosphate buffer), short-term stability (at 40 degrees /75% relative humidity for 3 mo) and drug-excipient interaction (IR spectroscopy). Among the two promising formulations, the formulation prepared by using 8% w/w of Plantago ovata mucilage and 60% w/w of microcrystalline cellulose emerged as the overall best formulation (t(50%) 3.3 min) based on the in vitro drug release characteristics compared to conventional commercial tablets formulation (t(50%) 17.4 min). Short-term stability studies on the formulations indicated that there are no significant changes in drug content and in vitro dispersion time (p<0.05).

Preparation and evaluation of orodispersible tablets of pheniramine maleate by effervescent method.

In the present work, orodispersible tablets of pheniramine maleate were designed with a view to enhance patient compliance by effervescent method. In the effervescent method, mixture of sodium bicarbonate and tartaric acid (each of 12% w/w concentration) were used along with super disintegrants, i.e., pregelatinized starch, sodium starch glycolate, croscarmellose sodium and crospovidone. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity and in vitro dispersion time. Based on in vitro dispersion time (approximately 60 s), three formulations were tested for in vitro drug release pattern (in pH 6.8 phosphate buffer), short-term stability (at 40+/-2 degrees /75+/-5% RH for 3 mo) and drug-excipient interaction (IR spectroscopy). Among three promising formulations, formulation ECP(4) containing 4% w/w crospovidone and mixture of sodium bicarbonate and tartaric acid (each of 12% w/w) emerged as the overall best formulation (t(70%) = 1.65 min) based on the in vitro drug release characteristics compared to commercial conventional tablet formulation. Short-term stability studies on the formulations indicated no significant changes in the drug content and in vitro dispersion time (P < 0.05).

Design of fast disintegrating tablets of prochlorperazine maleate by effervescence method.

In the present work, fast disintegrating tablets of prochlorperazine maleate were designed with a view to enhance patient compliance by effervescent method. In this method, mixtures of sodium bicarbonate and anhydrous citric acid in different ratios along with crospovidone (2-10% w/w), croscarmellose sodium (2-10% w/w) were used as superdisintegrants. Estimation of prochlorperazine maleate in the prepared tablet formulations was carried out by extracting the drug with methanol and measuring the absorbance at 254.5 nm. The prepared formulations were further evaluated for hardness, friability, drug content uniformity and in vitro dispersion time. Based on in vitro dispersion time (approximately 13-21 s), two promising formulations (one from each super-disintegrant) were tested for in vitro drug release pattern in pH 6.8 phosphate buffer, short-term stability (at 40 degrees /75% relative humidity for 3 mo) and drug-excipient interaction (IR spectroscopy). Among the two promising formulations, the formulation containing 10% w/w of crospovidone and mixture of 20% w/w sodium bicarbonate and 15% w/w of citric acid emerged as the overall best formulation (t(50%) 6 min) based on drug release characteristics in pH 6.8 phosphate buffer compared to commercial conventional tablet formulation (t(50%) 17.4 min). Short-term stability studies on the promising formulations indicated that there are no significant changes in drug content and in vitro dispersion time (p<0.05).

Formulation design and optimization of fast dissolving clonazepam tablets.

Fast dissolving tablets of clonazepam were prepared by direct compression method with a view to enhance patient compliance. A 3(2) full factorial design was applied to investigate the combined effect of two formulation variables: amount of crospovidone and microcrystalline cellulose. Crospovidone (2-8% w/w) was used as superdisintegrant and microcrystalline cellulose (20-40% w/w) was used as diluent, along with directly compressible mannitol to enhance mouth feel. The tablets were evaluated for hardness, friability, thickness, drug content uniformity, in vitro dispersion time, wetting time and water absorption ratio. Based on in vitro dispersion time (approximately 16 s); the formulation containing 2% w/w crospovidone and 40% w/w microcrystalline cellulose was found to be promising and tested for in vitro drug release pattern (in pH 6.8 phosphate buffer). Short-term stability (at 40 degrees /75% relative humidity for 3 mo) and drug-excipient interaction. Surface response plots are presented to graphically represent the effect of independent variables on the invitro dispersion time. The validity of the generated mathematical model was tested by preparing two extra-design checkpoints. The optimized tablet formulation was compared with conventional commercial tablet formulation for drug release profiles. This formulation showed nearly five-fold faster drug release (t(50%) 3.5 min) compared to the conventional commercial tablet formulation (t(50%) 16.4 min). Short-term stability studies on the formulation indicated that there are no significant changes in drug content and in vitro dispersion time (P<0.05).

Parenteral formulation of zopiclone.

The present study was undertaken with an intention to develop a stable and effective parenteral formulation, containing the drug zopiclone. Since zopiclone is a water insoluble drug, various methods such as co-solvency, pH control and hydrotrophy have been tried in order to enhance its solubility. When all these methods could not give adequate solubility enhancement of the drug, a hydrochloride salt was prepared, and it was found to be thermostable. Various batches of zopiclone hydrochloride injection formulation were prepared in order to assess the influence of light, atmospheric oxygen and antioxidant on the stability of the drug and the formulations were also subjected to accelerated stability testing in order to predict approximate shelf-life of the product.

Design and evaluation of fast dissolving tablets of clonazepam.

In the present work, fast dissolving tablets of clonazepam were prepared by direct compression method with a view to enhance patient compliance. Three super-disintegrants, viz., crospovidone, croscarmellose sodium and sodium starch glycolate in different ratios with microcrystalline cellulose (Avicel PH-102) along with directly compressible mannitol (Pearlitol SD 200) to enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity, wetting time, water absorption ratio and in vitro dispersion time. Based on in vitro dispersion time (approximately 13 s), three formulations were tested for the in vitro drug release pattern (in pH 6.8 phosphate buffer), short-term stability (at 40°/75% relative humidity for 6 mo) and drug-excipient interaction (IR spectroscopy). Among the three promising formulations, the formulation prepared by using 10% w/w of crospovidone and 35% w/w of microcrystalline cellulose emerged as the overall best formulation (t(50%) 1.8 min) based on the in vitro drug release characteristics compared to conventional commercial tablet formulation (t(50%) 16.4 min). Short-term stability studies on the formulations indicated that there were no significant changes in drug content and in vitro dispersion time (P<0.05).