A Contribution to the Manufacture of Diiodoquin TABLETS by Direct Compression

Abstract

Six direct compression vehicles and their binary blends in ratios of 1:1, 1:3 and 3:1 were investigated to compress diiodoquin directly into tablets. With respect to the mechanical properties of the produced tablets, Avicel, Celutab and 5TAR-x1500 were the suitable single vehicles for the manufacturing. Five vehicles, except STAR-x1500, produced tablets of fairly long disintegration times (120 min), while the other vehicle could not compress diiodoquin. The results shewed that blending of Avicel or Celutab with STAR-x1500 improved the physical standards of the produced tablets. Other than being a powerful disintegrant, STAR-x1500 could recover the disintegrating effect of Avicel. On the other hand, the reduction in disintegration times of the tablets compressed with STAR-/Celutab blends, was due to the incorporation of STAR-x in the formulations.

In such a case of noncompressible drug, a large concentration of a binary blended vehicle was needed to compress tablets of good physical characters. The least concentration needed to compress diiodoquin into tablets was not less than 42.0% w/w.     

Degradation Kinetics of Thiamine Hydrochloride in Directly Compressed Tablets I: Effect of Ageing Under Varying Temperature and Relative Humidity Conditions

Abstract

The degrzadation kinetics of thiamine hydrochloride in tablets directly compressed with either single or binary vehicles was studied. The presult shows that, tabletted vitamin stored at varying temperature conditions degraded by first order mechanism. The magnitude of the rate constant K, was dependent on the type and concentration of the vehicle used. The decomposition of vitamin B₁ at varying temperatures was amenable to Arrhenius treatment. The degradation pattern of the vitamin in Avicel or binary blend of Avicel with another vehicle, stored at varying relative humidity conditions deviated from a first order mechanism. There was indication that equilibrium phenomenon is involved in the degradation of the vitamin contained in these vehicles. A log-linear relationship was seen to exist between K, and moisture content of the tablet.     

A Contribution to the Manufacture of Diiodoquin TABLETS by Direct Compression

Six direct compression vehicles and their binary blends in ratios of 1:1, 1:3 and 3:1 were investigated to compress diiodoquin directly into tablets. With respect to the mechanical properties of the produced tablets, Avicel, Celutab and 5TAR-x1500 were the suitable single vehicles for the manufacturing. Five vehicles, except STAR-x1500, produced tablets of fairly long disintegration times (120 min), while the other vehicle could not compress diiodoquin. The results shewed that blending of Avicel or Celutab with STAR-x1500 improved the physical standards of the produced tablets. Other than being a powerful disintegrant, STAR-x1500 could recover the disintegrating effect of Avicel. On the other hand, the reduction in disintegration times of the tablets compressed with STAR-/Celutab blends, was due to the incorporation of STAR-x in the formulations.

In such a case of noncompressible drug, a large concentration of a binary blended vehicle was needed to compress tablets of good physical characters. The least concentration needed to compress diiodoquin into tablets was not less than 42.0% w/w.     

Preparation and Evaluation of Directly Compressed Medazepam Hydrochloride Tablets

Medazepam, the well known benzodiazepine derivative used as a transquillizer and in alcohol withdrawal, was prepared in directly compressed tablets. The directly compressible vehicles which were used. singly or in binary blends 1:1, were Avicel, Lactose, STA-Rx 1500 Emcompress and the recently introduced vehicle compactrol. It was found that Avicel and Emcompress represent the most suitable single vehicles used for the preparation of Medazepam hydrochloride tablets. In case of binary blends it was found that the best quality batches were prepared using Avicel Emcompress blend 1:1. Physical characteristics including uniformity of weight, thickness, hardness, friability were investigated for the prepared batches. The effect of directly compressible vehicle variation on the uniformity of drug content and the dissolution rates of Medazepam hydrochloride tablets was also studied.     

Dissolution of Directly Compressed Thiamine Hydrochloride Tablets

Abstract

Directly compressed thiamine hydrochloride tablets with varying concentrations of different vehicles as well as their binary blends, were prepared for this investigation. The results showed that, formulated tablets with avicel anhydrous lactose and celutab completely dissolved within short times. First order mechanism was reported for the tablets prepared with single vehicles. The dissolution rate constant “K”, was a function of disintegration constant “D” of the tablets by the relation In K = a + n In D. In addition to that, it is proved that, “K” of produced tablets of short disintegration times was a function of the contributed vehicle concentration “C” by the relation, I/K = A exp. + NC.

On the other hand, (T 50%) of thiamine hydrochloride in a given batch was a function of its disintegration time.     

Comparative Evaluation of Certain Excipients and their Binary Blends for Direct Compression Oxytetracycline Hydrochloride Tablets

Abstract

Five direct compression excipients as well as their binary blends in ratios of 1:1, 1:3 and 3:1 were comparatively evaluated to compress oxytetracycline hydrochloride into tablets. With respect to the mechanical properties of the produced tablets, Avicel PH101, Celutab and STAR-x1500 in this order, were the most suitable single excipients for the production. The results showed that the incorporation of a second excipient in the formulation changes the physical standards of the produced antibiotic tablets. It was found that not only the type of the incorporated excipient is effective but also, its concentration in the formula. The investigation proved that Avicel/STAR-x1500 blends in all different ratios followed by some blends of celutab with Avicel or STAR-x1500 were the best blended excipients to produce satisfactory antibiotic tablets.     

Degradation kinetics of thiamine hydrochloride in directly compressed tablets iii water vapour transmission through free and applied eudragit films

Abstract

Water vapour transmission through free and applied film of four Eudragit resins namely, E₁₀₀, L₁₀₀ and RS₁₀₀ to directly compressed thiamine hydrochloride tablets was investigated. The type of Eudragit film influenced both water vapour transmission and moisture absorption characteristics of the tablets compressed with either single or binary blend of vehicles. The moisture absorption rate constant K_a, for a given batch was found to be a function of vapour pressure, P, and film thickness, L. The relationship between K_a and either of these parameters is exponental and may be expressed as K_a = A exp (x/P) and K_a = K*_a exp (-x*L). In general, film coating with Eudragit resins affected the physical characteristics of the tablets. The rate of drug release, K has an exponentially relationship as K_e K_o exp (-c/L).     

Evaluation of Mujol as a Direct Compression Excipient in Oxytetracycline Hydrochloride Tablet Formulations

Abstract

The physical properties of oxytetracyc1ine hydrochloride tablets compressed with Musol, a new autocompressib1e vehicle obtained by chemical modification of an edible seed polysaccharide were studied, Avice1 PH 101, Fast-f1o lactose and Emcompress were used as basis for comparison.

With the exception of those tablets containing Emcompress, good disintegration and dissolution profiles were obtained in all the batches formulated. The dissolution characteristics of the tablets did not change significantly after storage in the dark at 30°C for 96 weeks.     

Degradation kinetics of thiamine hydrochloride in directly compressed tablets iii water vapour transmission through free and applied eudragit films

Water vapour transmission through free and applied film of four Eudragit resins namely, E₁₀₀, L₁₀₀ and RS₁₀₀ to directly compressed thiamine hydrochloride tablets was investigated. The type of Eudragit film influenced both water vapour transmission and moisture absorption characteristics of the tablets compressed with either single or binary blend of vehicles. The moisture absorption rate constant K_a, for a given batch was found to be a function of vapour pressure, P, and film thickness, L. The relationship between K_a and either of these parameters is exponental and may be expressed as K_a = A exp (x/P) and K_a = K*_a exp (-x*L). In general, film coating with Eudragit resins affected the physical characteristics of the tablets. The rate of drug release, K has an exponentially relationship as K_e K_o exp (-c/L).     

Compaction Behaviour of Musol,A New Direct Compression Vehicle

Abstract

The compaction characteristics of Musol, a new autocompressible vehicle derived through chemical modification of mucuna gum was investigated. Avicel PH 101, Zeparox and Encompress were used as reference tablet vehicles. Values of the mean yield stress derived from the analysis of Heckel plots indicate that Musol consolidates principally by plastic deformation, The effect of lubrication and recompression on friability, tensile strength and re-working potential of the tablets prepared with the vehicles were determined. While Avicel PH 101 yielded the strongest tablets, Musol showed the highest re-working potential for lubricated and un-lubricated slugs. On the basis of friability, tensile Values of strength and re-working potential, Musol than the grades of Zeparpx or Encompress performed better used in the study.     

The influence of tablet density on the human oral absorption of sustained release acetaminophen matrix tablets

Abstract

Low density bilayer compressed matrix tablets of acetaminophen were tested for in vitro dissolution and in vivo oral absorption. The upper layer contained a carbon dioxide-generating blend and the lower layer contained hydroxypropyl methylcellulose (HPMC) and acetaminophen. Carbon dioxide liberated by the action of the acidic dissolution medium on the upper layer is entrapped in the gelled hydrocolloid, providing buoyancy of the tablet and sustained release of the drug. For comparative purposes, similar but non-gas generating bilayer compressed matrix tablets were formulated and tested in vitro under the same conditions. These high density tablets were found to yield similar dissolution profiles as the low density tablets. The absorption characteristics of the bilayer compressed matrix tablets were compared with those of rapidly disintegrating acetaminophen tablets (TYLENOL® tablets, 500 mg) under fasted and fed conditions in six healthy subjects. Under fasted conditions, saliva profiles showed a rapid absorption for TYLENOL tablets but slower absorption for both compressed matrix tablets. Saliva profiles of TYLENOL® tablets under fed conditions were similar to those for the fasted case. In contrast, the peak saliva levels of acetaminophen for both compressed matrix tablets were significantly increased under fed conditions. The time to maximum saliva concentrations (Tmax) of all three dosage forms was not significantly affected by food intake. The relative bioavailability of the low density tablets under fasted and fed conditions was not significantly different from those of TYLENOL tablets, but vas significantly greater than that of high density tablets under fasted and fed conditions. A possibility exists that the buoyancy mechanism enabled the tablet to maintain more prolonged residence time in the gastrointestinal tract.     

Compaction Behaviour of Musol, A New Direct Compression Vehicle

The compaction characteristics of Musol, a new autocompressible vehicle derived through chemical modification of mucuna gum was investigated. Avicel PH 101, Zeparox and Encompress were used as reference tablet vehicles. Values of the mean yield stress derived from the analysis of Heckel plots indicate that Musol consolidates principally by plastic deformation, The effect of lubrication and recompression on friability, tensile strength and re-working potential of the tablets prepared with the vehicles were determined. While Avicel PH 101 yielded the strongest tablets, Musol showed the highest re-working potential for lubricated and un-lubricated slugs. On the basis of friability, tensile Values of strength and re-working potential, Musol than the grades of Zeparpx or Encompress performed better used in the study.     

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.     

Evaluation of Ludipress as a “Multipurpose Excipeent” for Direct Compression: Part I: Powder Characteristics and Tableting Properties

The powder characteristics and tableting properties of Ludipress, a lactose-based, free flowing granule containing povidone and crospovidone have been evaluated and compared to the physical blend of the base materials in Ludipress and to other filler/binders including Cellactose and Avicel PH 200.

The data were determined in order to evaluate flowability, bulk density, tapped density, Hausner ratio, angle of repose and particle size distribution. The particle morphology and constitution were examined using scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) was used to detect differences between lactose based products.

Several Ludipress samples exhibited a good batch-to-batch uniformity and flow characteristics compared to the physical blend and other excipients investigated.

The tableting parameters tested were crushing strength, friability and disintegration time. The ability to form coherent compacts was similar for Ludipress, Cellactose and Avicel PH 200, whereas tablets made from the physical blend resulted significantly softer. Determination of tablet disintegration time revealed a disintegration time minimum at about 100 MPa for Ludipress compacts. By augmenting compaction load from 100 to 185 MPa Cellactose showed an increase in disintegration time to more than 20 minutes. The disintegration times of Avicel PH 200 compacts were nearly constant and were also the shortest in the compaction load range examined.     

The influence of tablet density on the human oral absorption of sustained release acetaminophen matrix tablets

Low density bilayer compressed matrix tablets of acetaminophen were tested for in vitro dissolution and in vivo oral absorption. The upper layer contained a carbon dioxide-generating blend and the lower layer contained hydroxypropyl methylcellulose (HPMC) and acetaminophen. Carbon dioxide liberated by the action of the acidic dissolution medium on the upper layer is entrapped in the gelled hydrocolloid, providing buoyancy of the tablet and sustained release of the drug. For comparative purposes, similar but non-gas generating bilayer compressed matrix tablets were formulated and tested in vitro under the same conditions. These high density tablets were found to yield similar dissolution profiles as the low density tablets. The absorption characteristics of the bilayer compressed matrix tablets were compared with those of rapidly disintegrating acetaminophen tablets (TYLENOL® tablets, 500 mg) under fasted and fed conditions in six healthy subjects. Under fasted conditions, saliva profiles showed a rapid absorption for TYLENOL tablets but slower absorption for both compressed matrix tablets. Saliva profiles of TYLENOL® tablets under fed conditions were similar to those for the fasted case. In contrast, the peak saliva levels of acetaminophen for both compressed matrix tablets were significantly increased under fed conditions. The time to maximum saliva concentrations (Tmax) of all three dosage forms was not significantly affected by food intake. The relative bioavailability of the low density tablets under fasted and fed conditions was not significantly different from those of TYLENOL tablets, but vas significantly greater than that of high density tablets under fasted and fed conditions. A possibility exists that the buoyancy mechanism enabled the tablet to maintain more prolonged residence time in the gastrointestinal tract.     

Tabletting Properties of Musol; A New Direct Compression Vehicle

A new autocompressible vehicle, Musol, obtained by chemical modification of an edible seed polysaccharide was evaluated for direct compression properties, A Hausner ratio of 1,2 and percent compressibility of 16.7 obtained for Musol indicate that it has very good flow properties. Musol showed superiority over Avicel PH 101, USP Fast-Flo lactose, and Encompress when evaluated in terns of flow rake of powders and moisture sorption by both powders and their slugs, Compacts prepared with Musol were found to disintegrate by erosion and therefore did not perform as well as either alginic acid or Ac-disol in 250 mg Sulphadimidine tablets. However, good drug release was obtained from aspirin tablets containing 5% w/w Musol as a dry binder. The t₅₀, t₉₀ and Dissolution efficiency were as good as the values obtained with 5% w/w Avicel PH 101, A 50/50 blend of Musol and Avicel PH 101 surpassed other blends in performance.     

The effect of moisture on the physical characteristics of ranitidine hydrochloride tablets prepared by different binders and techniques

Abstract

The effect of moisture on the physical properties of ranitidine hydrochloride tablets prepared by direct-compression and by wet-granulation method using PVP or EC as binders was studied. Tablets adsorped moisture at 50 and 75 % RH (relative humidity) but lost moisture at 30% RH. Except storage at 75% RH, however, tablet volumes did not change significantly during the test period. Moisture sorption caused a decrease in strength of tablets except low humidity (30% RH). Also, the disintegration time of tablets showed a decrease at all conditions except 30% RH. Furthermore, generally dissolution profiles of tablets prepared by direct-compression and by ethyl cellulose remained unchanged. Changes in the binder type in the tablet formulations changed the water uptake properties and also the physical properties of tablets. Directly-compressed tablets were much susceptible to change caused by humidity than tablets prepared by wet-granulation.     

Investigation into The Yellowing on Aging of Sabril® Tablet Cores

Abstract

Uncoated Sabril® tablet cores under long term storage become slightly discolored from the initial white to a yellowish off-white color. In order to ensure the aesthetics of the product, Sabril tablet cores are film coated with an opaque white coating. The nature of this yellowing reaction was of interest even though discolored tablets showed no significant loss of potency on assay. Excipient compatibility studies showed that the vigabatrin active in Sabril mixed with Avicel (microcrystalline cellulose) in the presence of moisture also became off-colored when stressed at elevated temperatures.

The nature of the discoloration in aged Sabril core tablets was investigated. Chromatographic and spectroscopic data indicate that the source of this color comes from the Maillard Reaction between vigabatrin and Avicel which results in a multitude of products analogous to “browning reactions” of food products. A gravimetric determination of the leached colored products from 7 year old Sabril core tablets gave a residue of less than 0.1% relative to vigabatrin. Furthermore, based on spectroscopy, most of this residue was found to be povidone, an excipient in the tablets which was isolated along with the colored substances.

Therefore, the colored products identified in the core of Sabril tablets stored for an extended period of time represent only minor impurities. Their formation through aging arises via the Maillard Reaction and would only constitute a matter of aesthetics. The latter problem is avoided by the currently employed film coating process.

Similar reactions could be predicted for other drugs having amine functional groups if they are formulated with microcrystalline cellulose or reducing sugars.     

Compression of Miczocwsules II: Effect of Excipients and Pressure on Physical Propertise accordance with their physical properties

Abstract

Dmg-resin carplexes were microencapsulated and cmpressed into tablets with the aid of various excipients. Carpression of the microcamules at pressures ranging fran 35 MPa to 281 MPa produced tablets of acceptable physical properties only with Avicel. When Rdex or Fast Flo Lactose were used an unacceptably high tablet friability was seen. The tablet porosities varied in     

Evaluation of Ludipress as a “Multipurpose Excipeent” for Direct Compression: Part I: Powder Characteristics and Tableting Properties

The powder characteristics and tableting properties of Ludipress, a lactose-based, free flowing granule containing povidone and crospovidone have been evaluated and compared to the physical blend of the base materials in Ludipress and to other filler/binders including Cellactose and Avicel PH 200.

The data were determined in order to evaluate flowability, bulk density, tapped density, Hausner ratio, angle of repose and particle size distribution. The particle morphology and constitution were examined using scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) was used to detect differences between lactose based products.

Several Ludipress samples exhibited a good batch-to-batch uniformity and flow characteristics compared to the physical blend and other excipients investigated.

The tableting parameters tested were crushing strength, friability and disintegration time. The ability to form coherent compacts was similar for Ludipress, Cellactose and Avicel PH 200, whereas tablets made from the physical blend resulted significantly softer. Determination of tablet disintegration time revealed a disintegration time minimum at about 100 MPa for Ludipress compacts. By augmenting compaction load from 100 to 185 MPa Cellactose showed an increase in disintegration time to more than 20 minutes. The disintegration times of Avicel PH 200 compacts were nearly constant and were also the shortest in the compaction load range examined.