Formulation and evaluation of rapidly disintegrating fenoverine tablets: effect of superdisintegrants

The objective of this study was to formulate directly compressible rapidly disintegrating tablets of fenoverine with sufficient mechanical integrity, content uniformity, and acceptable palatability to assist patients of any age group for easy administration. Effect of varying concentrations of different superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate on disintegration time was studied. Tablets were evaluated for weight variation, thickness, hardness, friability, taste, drug content, in vitro and in vivo disintegration time, and in vitro drug release. Other parameters such as wetting time, water absorption ratio ('R'), and drug-excipient compatibility were also evaluated. The disintegration time of the best rapidly disintegrating tablet formulation among those tested was observed to be 15.9 sec in vitro and 37.16 sec in vivo. Good correlation was observed between disintegration time and 'R' for each of the three superdisintegrants at the concentrations studied. Considering the 'R' values and disintegration time, crospovidone was significantly superior (p < 0.05) compared to the other superdisintegrants tested. Release of drug was faster from formulations containing 6% crospovidone (CP 6) compared to the marketed fenoverine (Spasmopriv(R)) capsules. Similarity factor 'f(2)' (51.5) between dissolution profiles of the rapidly disintegrating tablet formulation CP 6 and the marketed formulation indicated that the two dissolution profiles were similar. Differential scanning calorimetric studies did not indicate any excipient incompatibility, either during mixing or after compression. In conclusion, directly compressible rapidly disintegrating tablets of fenoverine with lower friability, acceptable taste, and shorter disintegration times were obtained using crospovidone and other excipients at optimum concentrations.     

Formulation and Evaluation of Rapidly Disintegrating Fenoverine Tablets: Effect of Superdisintegrants

The objective of this study was to formulate directly compressible rapidly disintegrating tablets of fenoverine with sufficient mechanical integrity, content uniformity, and acceptable palatability to assist patients of any age group for easy administration. Effect of varying concentrations of different superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate on disintegration time was studied. Tablets were evaluated for weight variation, thickness, hardness, friability, taste, drug content, in vitro and in vivo disintegration time, and in vitro drug release. Other parameters such as wetting time, water absorption ratio (‘R’), and drug-excipient compatibility were also evaluated. The disintegration time of the best rapidly disintegrating tablet formulation among those tested was observed to be 15.9 sec in vitro and 37.16 sec in vivo. Good correlation was observed between disintegration time and ‘R’ for each of the three superdisintegrants at the concentrations studied. Considering the ‘R’ values and disintegration time, crospovidone was significantly superior (p < 0.05) compared to the other superdisintegrants tested. Release of drug was faster from formulations containing 6% crospovidone (CP 6) compared to the marketed fenoverine (Spasmopriv®) capsules. Similarity factor ‘f₂’ (51.5) between dissolution profiles of the rapidly disintegrating tablet formulation CP 6 and the marketed formulation indicated that the two dissolution profiles were similar. Differential scanning calorimetric studies did not indicate any excipient incompatibility, either during mixing or after compression. In conclusion, directly compressible rapidly disintegrating tablets of fenoverine with lower friability, acceptable taste, and shorter disintegration times were obtained using crospovidone and other excipients at optimum concentrations.     

A Study of the Chemical and Physical Stability of Ascorbic Acid,Folic Acid,and Thiamine Hydrochloride Tablets Formulated with Emcompress Standard

Abstract

Tablets which were prepared from separate formulations of Emcompress Standard^R, a commercially available directly compressible granulation, with ascorbic acid, folic acid, and thiamine hydrochloride were subjected to accelerated aging conditions and studied for chemical stability and such physical parameters as hardness, friability, and disintegration time. Other physical factors which could affect the interpretation of the data, such as moisture content, particle size distribution, angle of repose, weight variation, and hardness were also studied using fresh samples.

Accelerated aging showed that the ascorbic acid formulation was chemically unstable; the tablets became soft, the frability increased markedly, and the disintegration time decreased. The folic acid formulation was chemically stable, but the tablets became soft, the friability increased, and disintegration time increased. The thiamine hydrochloride formulation was also chemically stable—the tablets became soft, the disintegration time decreased, and the friability increased.     

Formulation factors affecting drug release from poly(lactic acid) (PLA) microcapsule tablets

A sustained-release (SR) formulation of phenobarbital (PB) microcapsule tablet was prepared using low molecular weight (MW) DL- and high MW L-poly(lactic acid) (PLA) polymer. Microencapsulation of PB showed a unimodal size distribution (375 to 550 microns) of the microcapsules with high loading capacity (> 84%). Drug release from the microcapsule was influenced by the polymer ratios and increased with an increase in L-PLA amount. Microcapsules and physical mixtures of PB and the PLA were directly compressed independently to form microcapsule and matrix tablets, respectively. Drug release from the microcapsule tablets was significantly lowered (p < .001) compared to matrix tablets or free microcapsule (free microcapsule > matrices > microcapsule tablets). We also investigated the effect of tablet adjuvants, compression pressures, and microcapsule loading on the tablet performance in terms of friability, hardness, porosity, tensile strength, and the release kinetics of PB. The drug release rate increased with increasing compression pressure in the case of Emcompress or lactose, but not Avicel. The drug release rate was three- to fivefold increased with sodium starch glycolate compared to tablets without a disintegrant. With an increase in microcapsule loading, a decrease in the drug release rate was observed; however, the tablet performance remained satisfactory. The morphology of the microcapsules was monitored microscopically after the dissolution and the disintegration of tablets. The drug release accelerated with compression pressures and microcapsule loading from the tablets due to mechanical destruction of the microcapsule wall, which was more clearly seen after disintegration and dissolution of the tablets. Our data suggest that the PLA microcapsule can be tableted to make a SR product without significantly affecting its release kinetics.     

The Effect of Some Surfactants on the in- Vitro Properties of Double Compressed Tablets

The effect of different types and concentrations of some surface active agents as well as the method of surfactant incorporation on the in - vitro properties of aspirin tablets as a model for double compressed tablets was studied. The formulated tablets were evaluated using the U. S. P. official tests and some other selected non-official tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. Incorporation of a low concentration (0.2 % w/w) of surface active agents i n the formulation of tablets decreased the disintegration time but did not affect their dissolution rate. Higher concentrations of surface active agents retarded the dissolutiono of tablets. Non ionic surfactants showed higher regarding effect than ionic surfactants . Changing the method of surfactant incorporation did not greatly affect the dissolution rate of tablets.     

A Comparative Evaluation of Some Starches as Disintegrants for Double Compressed Tablets

The effect of different types and concentrations of some starches as disintegrants on the properties of aspirin tablets as a model for double compressed tablets was studied. The formulated tablets were evaluated using the U.S.P. official tests and some other selected nonofficial tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. Maize starch was found to be the most suitable disintegrant for the formulation of double compressed tablets while rice starch was the worst disintegrant, in this study, as it significantly increased the hardness of tablets and showed a prolonged disintegration time as well as a poor dissolution rate. increasing the starch content of tablets resulted in a marked increase in their dissolution rate.     

Preparation and in vitro evaluation of controlled release hydrophilic matrix tablets of ketorolac tromethamine using factorial design

Controlled release matrix tablets of ketorolac tromethamine (KT) were prepared by direct compression technique using cellulose derivatives as hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), and carboxymethyl cellulose (CMC) in different concentrations (10-20%). The effect of polymer type and concentration was investigated on drug release by 2(3) factorial design. For the quality control of matrix tablets, weight deviation, hardness, friability, diameter-height ratio, content uniformity of KT, and in vitro dissolution technique were performed. UV Spectrophotometric method was used to detection of KT in matrix tablets. This method was validated. Dissolution profiles of the formulations were plotted and evaluated kinetically. An increase in polymer content resulted with a slow release rate of drug as was expected. According to the dissolution results, tablets prepared with HPMC + HEC + CMC (F1 and F8) were found to be the most suitable formulation for KT. About 99.27% KT was released from F8 in 7 h.     

The Effect of Some Surfactants on the in- Vitro Properties of Double Compressed Tablets

Abstract

The effect of different types and concentrations of some surface active agents as well as the method of surfactant incorporation on the in - vitro properties of aspirin tablets as a model for double compressed tablets was studied. The formulated tablets were evaluated using the U. S. P. official tests and some other selected non-official tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. Incorporation of a low concentration (0.2 % w/w) of surface active agents i n the formulation of tablets decreased the disintegration time but did not affect their dissolution rate. Higher concentrations of surface active agents retarded the dissolutiono of tablets. Non ionic surfactants showed higher regarding effect than ionic surfactants. Changing the method of surfactant incorporation did not greatly affect the dissolution rate of tablets.     

Chitosan and Sodium Sulfate as Excipients in the Preparation of Prolonged Release Theophylline Tablets

The major objectives of this study were to monitor the effect of cross-linking of cationic chitosan in acidic media with sulfate anion during granules preparation by wet granulation method prior to tableting using theophylline (TPH) as a model drug. The prepared granules and the compressed tablets were subjected to in vitro evaluation. The properties of the prepared matrix granules and the compressed tablets were dependent on chitosan:sodium sulfate weight ratios, chitosan content, and molecular weight of chitosan. The prepared granules of all batches showed excellent to passable flowability and were suitable for compression into tablets. Most of the granules were hard and expected to withstand handling during the subsequent compression into tablets. Granules with high friabilities were only those prepared with a high amount of sodium sulfate or low amount of chitosan. Compression of granule batches yield nondisintegrating tablets that showed a decrease in tensile strength with the increase of sodium sulfate content at high chitosan:sodium sulfate weight ratio or with decrease of chitosan content. On the other hand, friability of tablets was increased in the presence of an excessive amount of sodium sulfate and low chitosan content as observed with granules. Slow TPH release from the formulated tablets was achieved at 1:0.5 and 1:1 chitosan:sodium sulfate weight ratios where all or most of the cationic chitosan and sulfate anions were used in a cross-linking reaction during wet granulation. Ratios of 1:2 and 1:3 showed fast drug release, which support the hypothesis that excessive unreacted water-soluble sodium sulfate might increase the porosity of the nondesintegrating tablets during dissolution. Slow drug release was also obtained with high molecular weight chitosan, whereas changing the hardness of the tablets did not significantly change the release profile of the drug as long as the tablets are intact during dissolution. Furthermore, slow drug release was observed as the total amount of chitosan was increased in the formulated tablets. A comparative in vivo study between the chosen formulated tablets (1:1 chitosan:sodium sulfate ratio that contains 10% high molecular weight chitosan) and the commercial Quibron® tablets indicated prolonged appearance of the drug in dogs' plasma for both formulations with no significant differences (p > 0.05) in rate and extent of drug absorption. The formulated tablets showed 103.16% bioavailability relative to that of the commercial tablets.     

Chitosan and sodium sulfate as excipients in the preparation of prolonged release theophylline tablets

The major objectives of this study were to monitor the effect of cross-linking of cationic chitosan in acidic media with sulfate anion during granules preparation by wet granulation method prior to tableting using theophylline (TPH) as a model drug. The prepared granules and the compressed tablets were subjected to in vitro evaluation. The properties of the prepared matrix granules and the compressed tablets were dependent on chitosan:sodium sulfate weight ratios, chitosan content, and molecular weight of chitosan. The prepared granules of all batches showed excellent to passable flowability and were suitable for compression into tablets. Most of the granules were hard and expected to withstand handling during the subsequent compression into tablets. Granules with high friabilities were only those prepared with a high amount of sodium sulfate or low amount of chitosan. Compression of granule batches yield nondisintegrating tablets that showed a decrease in tensile strength with the increase of sodium sulfate content at high chitosan:sodium sulfate weight ratio or with decrease of chitosan content. On the other hand, friability of tablets was increased in the presence of an excessive amount of sodium sulfate and low chitosan content as observed with granules. Slow TPH release from the formulated tablets was achieved at 1:0.5 and 1:1 chitosan:sodium sulfate weight ratios where all or most of the cationic chitosan and sulfate anions were used in a cross-linking reaction during wet granulation. Ratios of 1:2 and 1:3 showed fast drug release, which support the hypothesis that excessive unreacted water-soluble sodium sulfate might increase the porosity of the nondesintegrating tablets during dissolution. Slow drug release was also obtained with high molecular weight chitosan, whereas changing the hardness of the tablets did not significantly change the release profile of the drug as long as the tablets are intact during dissolution. Furthermore, slow drug release was observed as the total amount of chitosan was increased in the formulated tablets. A comparative in vivo study between the chosen formulated tablets (1:1 chitosan:sodium sulfate ratio that contains 10% high molecular weight chitosan) and the commercial Quibron tablets indicated prolonged appearance of the drug in dogs' plasma for both formulations with no significant differences (p > 0.05) in rate and extent of drug absorption. The formulated tablets showed 103.16% bioavailability relative to that of the commercial tablets.     

Preparation and In Vitro Evaluation of Controlled Release Hydrophilic Matrix Tablets of Ketorolac Tromethamine Using Factorial Design

Controlled release matrix tablets of ketorolac tromethamine (KT) were prepared by direct compression technique using cellulose derivatives as hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), and carboxymethyl cellulose (CMC) in different concentrations (10–20%). The effect of polymer type and concentration was investigated on drug release by 2³ factorial design. For the quality control of matrix tablets, weight deviation, hardness, friability, diameter–height ratio, content uniformity of KT, and in vitro dissolution technique were performed. UV Spectrophotometric method was used to detection of KT in matrix tablets. This method was validated. Dissolution profiles of the formulations were plotted and evaluated kinetically. An increase in polymer content resulted with a slow release rate of drug as was expected. According to the dissolution results, tablets prepared with HPMC + HEC + CMC (F1 and F8) were found to be the most suitable formulation for KT. About 99.27% KT was released from F8 in 7 h.     

A Comparative Evaluation of Some Starches as Disintegrants for Double Compressed Tablets

Abstract

The effect of different types and concentrations of some starches as disintegrants on the properties of aspirin tablets as a model for double compressed tablets was studied. The formulated tablets were evaluated using the U.S.P. official tests and some other selected nonofficial tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. Maize starch was found to be the most suitable disintegrant for the formulation of double compressed tablets while rice starch was the worst disintegrant, in this study, as it significantly increased the hardness of tablets and showed a prolonged disintegration time as well as a poor dissolution rate. increasing the starch content of tablets resulted in a marked increase in their dissolution rate.     

Fast relief from migraine attacks using fast-disintegrating sublingual zolmitriptan tablets

Zolmitriptan is a potent molecule for treatment of migraine. Its current oral therapies present drawbacks such as slow onset of action, low bioavailability and large inter-subject variability. Fast disintegrating sublingual zolmitriptan tablet (FDST) using freeze-drying technique has been developed to enhance tablet disintegration and dissolution with the intention of speeding drug absorption and onset of effect, hence mitigating the effects on the gastrointestinal dysmotility that typically accompanies the migraine attack. The FDSTs were prepared using different concentrations of gelatin as binder and mannitol or L-alanine as matrix supporting/disintegration enhancing agents. The effect of formulation variables on the physicochemical and solid-state properties, as well as the dissolution behaviour of the tablets, was studied. The formulated FDSTs disintegrated within 30 s and showed significantly faster dissolution rate of zolmitriptan compared to the zolmitriptan oral tablet. Tablet containing 2% gelatin and mannitol showed acceptable weight variation, drug content and friability values. Furthermore, it had a low in-vitro and in-vivo disintegration time (11 s) and it reached 100% of drug release within 30 s. This sublingual formulation gave faster and higher zolmitriptan plasma concentration in rabbits compared to the oral zolmetriptan market product. Zolmitriptan FDST may therefore constitute an advance in the management of acute migraine attacks.     

Evaluation of Commercial Metronidazole Tablets

Six commercial brands of metronidazole tablets from different manufacturers were elected for this study. The tablets were evaluated using the official and non-official tests of U.S.P. XX. These tests include: uniformity of weight, hardness, friability, disintegration time and dissolution rate. The results obtained showed that most of these brands passed the U.S.P. requirements. The dissolution rate studies showed a great differences in drug release characteristics between brands and also between batches of the same brand. Studies on drug content for each metronidazole brand showed a great variation between the brands and to a less extent within the different batches of the same brand. For the intense bitter taste of metronidazole, a trial was done to prepare it in the form of capsule. The dissolution rate of such capsule was much better than all the commercial tablets studied.     

The Effect of Lubricants on the Properties of Chloroquine Phosphate Tablets

Abstract

The properties of tablets prepared from different size fractions of chloroquine phosphate granules using different lubricants were evaluated. Lubricants used were magnesium stearate, stearic acid and talc, tablet properties studied include weight variation, crushing strength, friability and disintegration time

The effects obtained were largely dependent on the type and concentration of lubricant. Generally, as granule size increased, tablets were found to show increased weight variation, decreased hardness and increased friability. With tablets containing talc as lubricant, disintegration time was shown to decrease with increase in granule size.

There appears to be an optimum lubricant concentration for the compression of different granule size fractions.     

Evaluation of mucilage of Hibiscus rosasinensis Linn as rate controlling matrix for sustained release of diclofenac

This article reports the exploitation of novel hydrophilic excipient, that is, mucilage from Hibiscus rosasinensis Linn, for the development of sustained release tablet. Swelling ratio and flow properties analyses of dried mucilage powder were carried out. A 3(2) full factorial design was used. In factorial design, amounts of dried mucilage and dibasic calcium phosphate (DCP) were taken as independent factors and percentage drug release in 60 and 300 min and time for 80% drug release as dependent variables. Matrix tablet containing dried mucilage and diclofenac sodium (DS) was prepared through direct compression techniques. DS tablets were evaluated for hardness, friability, weight variation, in vitro drug release and water uptake, and mass loss study. The dried mucilage powder shows superior swelling capacity and excellent flow properties. Prepared tablets have acceptable hardness, friability, and uniformity in weight. It was found that batch HD8 fulfills all selected criteria. Drug release kinetics from these formulations corresponded best to the zero-order kinetics. Water uptake was independent whereas mass loss was dependent on agitation speed. The concept of similarity factor (f(2)) was used to prove similarity of dissolution profile in distilled water and phosphate buffer and was found to be 90.68. It was concluded that mucilage can be used as release-retarding agent for 12 h when the drug-mucilage ratio was 1:1.5. So, matrix tablet containing dried mucilage is most suitable for sustained release of DS.     

Evaluation of Mucilage of Hibiscus rosasinensis Linn as Rate Controlling Matrix for Sustained Release of Diclofenac

This article reports the exploitation of novel hydrophilic excipient, that is, mucilage from Hibiscus rosasinensis Linn, for the development of sustained release tablet. Swelling ratio and flow properties analyses of dried mucilage powder were carried out. A 3² full factorial design was used. In factorial design, amounts of dried mucilage and dibasic calcium phosphate (DCP) were taken as independent factors and percentage drug release in 60 and 300 min and time for 80% drug release as dependent variables. Matrix tablet containing dried mucilage and diclofenac sodium (DS) was prepared through direct compression techniques. DS tablets were evaluated for hardness, friability, weight variation, in vitro drug release and water uptake, and mass loss study. The dried mucilage powder shows superior swelling capacity and excellent flow properties. Prepared tablets have acceptable hardness, friability, and uniformity in weight. It was found that batch HD8 fulfills all selected criteria. Drug release kinetics from these formulations corresponded best to the zero-order kinetics. Water uptake was independent whereas mass loss was dependent on agitation speed. The concept of similarity factor (f₂) was used to prove similarity of dissolution profile in distilled water and phosphate buffer and was found to be 90.68. It was concluded that mucilage can be used as release-retarding agent for 12 h when the drug–mucilage ratio was 1:1.5. So, matrix tablet containing dried mucilage is most suitable for sustained release of DS.     

Fast relief from migraine attacks using fast-disintegrating sublingual zolmitriptan tablets

Zolmitriptan is a potent molecule for treatment of migraine. Its current oral therapies present drawbacks such as slow onset of action, low bioavailability and large inter-subject variability. Fast disintegrating sublingual zolmitriptan tablet (FDST) using freeze-drying technique has been developed to enhance tablet disintegration and dissolution with the intention of speeding drug absorption and onset of effect, hence mitigating the effects on the gastrointestinal dysmotility that typically accompanies the migraine attack. The FDSTs were prepared using different concentrations of gelatin as binder and mannitol or L-alanine as matrix supporting/disintegration enhancing agents. The effect of formulation variables on the physicochemical and solid-state properties, as well as the dissolution behaviour of the tablets, was studied. The formulated FDSTs disintegrated within 30 s and showed significantly faster dissolution rate of zolmitriptan compared to the zolmitriptan oral tablet. Tablet containing 2% gelatin and mannitol showed acceptable weight variation, drug content and friability values. Furthermore, it had a low in-vitro and in-vivo disintegration time (11 s) and it reached 100% of drug release within 30 s. This sublingual formulation gave faster and higher zolmitriptan plasma concentration in rabbits compared to the oral zolmetriptan market product. Zolmitriptan FDST may therefore constitute an advance in the management of acute migraine attacks.     

Evaluation of Commercial Metronidazole Tablets

Abstract

Six commercial brands of metronidazole tablets from different manufacturers were elected for this study. The tablets were evaluated using the official and non-official tests of U.S.P. XX. These tests include: uniformity of weight, hardness, friability, disintegration time and dissolution rate. The results obtained showed that most of these brands passed the U.S.P. requirements. The dissolution rate studies showed a great differences in drug release characteristics between brands and also between batches of the same brand. Studies on drug content for each metronidazole brand showed a great variation between the brands and to a less extent within the different batches of the same brand. For the intense bitter taste of metronidazole, a trial was done to prepare it in the form of capsule. The dissolution rate of such capsule was much better than all the commercial tablets studied.     

In-vitro evaluation of sustained-release dyphylline tablets

Dyphylline tablets were prepared by direct compression of mixtures of the drug, emcompress and different ratios of hydroxypropyl methylcellulose (HPMC) or cellulose acetate phthalate (CAP). Physical properties of the prepared tablets and the drug release in 0.1 N HC1 and phosphate buffer, pH 7.4 were investigated.

All tablets were found to satisfy the USP requirements regarding content, weight uniformity and friability. Hardness was greatly enhanced and thickness was slightly increased by increasing the polymer ratio in tablet formulations. Disintegration time of the dyphylline tablets was delayed by the presence of either HPMC or CAP and there was a direct relationship between the polymer ratio and the disintegration time. Considerable retardation in the rate and extent of drug release from the prepared tablets in both dissolution liquids was observed. As the polymer ratio increased in the tablet formulations, the drug release was significantly inhibited.