Effects of Hydrophilic Excipients and Compression Pressure on Physical Properties and Release Behavior of Aspirin-Tableted Microcapsules

Aspirin ethylcellulose microcapsules were tableted by compression with or without excipients (lactose or polyvinylpyrrolidone [PVP]). The effects of the amount of the excipients and microcapsule size on the crushing strength and release rate of aspirin from tableted microcapsules were investigated. Tablets without excipients had a crushing strength that was independent of the applied pressure and microcapsule size. An increase in compression pressure from 15 to 60 MPa resulted in an increase in the crushing strength of tablets containing 20% or 40% w/w lactose, but the reverse results were obtained for the tableted microcapsules containing 20% or 40% w/w PVP. Results showed that the release rate of aspirin from microcapsules containing lactose or PVP was independent of the compression pressure with the exception of tablets containing 40% w/w lactose. In vitro release profiles of aspirin from tableted microcapsules containing lactose or PVP showed that increasing the concentration of the excipients resulted in an increase in the release rate of aspirin. Values of n were changed by the compression pressure and the added excipients.     

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.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^-2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Abstract

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^?2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Tablet Properties and Dissolution Characteristics of Compressed Cellulose Acetate Butyrate Microcapsules Containing Succinyl Sulfathiazole

Cellulose acetate butyrate microcapsules of succinyl sulfathiazole were prepared by a modified emulsion-solvent evaporation method and formulated for compression with microcrystalline cellulose and carboxymethyl starch. Tablet hardness decreased and friability increased as microcapsule content increased. Formulations containing up to 50% microcapsules produced satisfactory tablets, but at 70% microcapsules, the tablets were unacceptably fragile. Variation of microcapsule size fraction from 75 μm up to 428 μm had only a small effect on tablet properties when formulated at the 40% level. Tablet hardness increased with increasing compression pressure from 1.9 kg at 17.6 MPa to 14.9 kg at 210.7 MPa. Dissolution properties of the microcapsules were essentially unchanged at compression pressures up to 351 MPa with T_50% values ranging from 121 to 132 minutes. Uncompressed microcapsules had a T_50% value of 130 minutes.     

Tablet Properties and Dissolution Characteristics of Compressed Cellulose Acetate Butyrate Microcapsules Containing Succinyl Sulfathiazole

Abstract

Cellulose acetate butyrate microcapsules of succinyl sulfathiazole were prepared by a modified emulsion-solvent evaporation method and formulated for compression with microcrystalline cellulose and carboxymethyl starch. Tablet hardness decreased and friability increased as microcapsule content increased. Formulations containing up to 50% microcapsules produced satisfactory tablets, but at 70% microcapsules, the tablets were unacceptably fragile. Variation of microcapsule size fraction from 75 μm up to 428 μm had only a small effect on tablet properties when formulated at the 40% level. Tablet hardness increased with increasing compression pressure from 1.9 kg at 17.6 MPa to 14.9 kg at 210.7 MPa. Dissolution properties of the microcapsules were essentially unchanged at compression pressures up to 351 MPa with T_50% values ranging from 121 to 132 minutes. Uncompressed microcapsules had a T_50% value of 130 minutes.     

Effect of Some Excipjents and Compression Pressure on the Adhesion of Aqueous-Based Hydroxypropyl Methylcellulose Film Coatings to Tablet Surface

The adhesion between aqueous-based hydroxypropyl methylcellulose (HPMC) films and tablet surface was evaluated using a Lloyd LRX materials testing machine. Special attention was paid to the effects of compression pressure and the excipients (microcrystalline cellulose, lactose and a commercial combination of lactose and cellulose (Cellactose^R)) on the adhesion properties of the film.

The adhesion of HPMC films was the lowest for the tablets containing lactose as a diluent and the highest for the tablets containing microcrystalline cellulose. The adhesion to Cellactose^R-based tablets increased with increasing compression pressure. With microcrystalline cellulose (MCC) and lactose, the effect of compression pressure on film adhesion was not so clear. The increase in concentration of a hydrophopic lubricant, magnesium stearate, decreased the adhesion between the films and tablets cores. The greatest decrease was observed with the MCC tablets.

Furthermore the results showed that, the film coating increased clearly the mechanical strength of the tablets, depending on the excipient, the compression pressure and amount of magnesium stearate.     

Effect of Some Excipjents and Compression Pressure on the Adhesion of Aqueous-Based Hydroxypropyl Methylcellulose Film Coatings to Tablet Surface

Abstract

The adhesion between aqueous-based hydroxypropyl methylcellulose (HPMC) films and tablet surface was evaluated using a Lloyd LRX materials testing machine. Special attention was paid to the effects of compression pressure and the excipients (microcrystalline cellulose, lactose and a commercial combination of lactose and cellulose (Cellactose^R)) on the adhesion properties of the film.

The adhesion of HPMC films was the lowest for the tablets containing lactose as a diluent and the highest for the tablets containing microcrystalline cellulose. The adhesion to Cellactose^R-based tablets increased with increasing compression pressure. With microcrystalline cellulose (MCC) and lactose, the effect of compression pressure on film adhesion was not so clear. The increase in concentration of a hydrophopic lubricant, magnesium stearate, decreased the adhesion between the films and tablets cores. The greatest decrease was observed with the MCC tablets.

Furthermore the results showed that, the film coating increased clearly the mechanical strength of the tablets, depending on the excipient, the compression pressure and amount of magnesium stearate.     

Pharmaceutical design of a new lactose-free coprocessed excipient: application of hydrochlorothiazide as a low solubility drug model

Most co-processed excipients used in direct-compression tablets contain lactose, which prevents lactose-intolerant patients from taking such tablets. Therefore, a novel lactose-free co-processed excipient for direct compression tablets has been prepared. Microcrystalline cellulose and dicalcium phosphate dehydrate were used as primary excipients which underwent a wet granulation process and factorial experiment in order to ascertain the best prototype. Finally, the best two prototypes were added to hydrochlorothiazide, which has chosen as the model drug because of its low solubility. An extensive characterization of the new excipient as well as the drug loaded tablets is reported. Our results show adequate parameters (rheological and compression behavior, uniformity of weight, disintegration, friability, crushing force and cohesion index). Moreover, the biopharmaceutical profile was evaluated; the tablets exhibits a Weibull kinetic function and fast drug release.     

Preparation and characterization and release properties of Eudragit RS based ibuprofen pellets prepared by extrusion spheronization: effect of binder type and concentration

Objective: The effects of type and concentration of binding agent on properties of Eudragit RS based pellets were studied.

Materials and methods: Pellets containing ibuprofen (60%), Eudragit RS (30%), Avicel (10%) were prepared by extrusion spheronization. PVP K30, PVP K90, HPMC 6cp, HPMC K100LV or HPMC K4M were used as binders in concentrations of 2, 4 or 6% based on the total weight of formulation. The process efficiency, pellet shape, size distribution, crushing strength, elastic modulus and drug release were examined. The effect of curing on pellet properties was also investigated.

Results: The process of extrusion spheronization became difficult with increase in binder viscosity and/or concentration. An increase in binder viscosity and/or concentration resulted in reduction in the yield of pellets, wider particle size distribution and departure from spherical shape especially in the case of HPMC binder. The crushing strength and elastic modulus of pellets decreased with increase in PVPs concentration. However this was not the case for pellets containing HPMCs. Drug release rate increased as the concentration of binder increased. Pellets containing 2%w/w of PVP K30 showed the slowest release rate. For those pellets with brittle nature, curing changed the behavior of pellet under mechanical test to plastic deformation. Yield point and elastic modulus of all formulations decreased after curing. Curing decreased the drug release rate.

Conclusion: Binder type and concentration significantly affected the properties of pellets. For production of sustained release ibuprofen Eudragit RS based pellets lower viscosity binders (PVP K30) with concentrations less than 4%w/w was optimum.     

Evaluation of the effects of khaya gum on the mechanical and release properties of paracetamol tablets

A study of the comparative effects of khaya gum and two standard binding agents-polyvinylpyrrolidone (PVP) and gelatin--on crushing strength and friability, and the disintegration and dissolution characteristics of paracetamol tablets was made. The crushing strength-friability ratio (CSFR), the disintegration times, D, and the dissolution times t50, t90, and t1 (derived from the equation of Noyes and Whitney), all increased with an increase in binder concentration; however, the dissolution rate constants, k1 and k2, decreased. The ranking for the values of CSFR for tablets containing the different binders was PVP > gelatin > khaya gum. The ranking for D and the dissolution times was gelatin > khaya gum > PVP, whereas the ranking for the dissolution rate constants was PVP > khaya gum > gelatin. There were significant linear correlations between CSFR, D, t50, t90, and t1 for the tablets. There were also significant correlations between k1 and D, t50, t90, and t1, and between k2 and t90. The results suggest that khaya gum could be useful as an alternative binding agent to produce tablets with particular mechanical strength and drug release profiles.     

Comparison Studies on the Percolation Thresholds of Binary Mixture Tablets Containing Excipients of Plastic/Brittle and Plastic/Plastic Deformation Properties

Percolation theory has been used with great interest in understanding the design and characterization of dosage forms. In this study, work has been carried out to investigate the behavior of binary mixture tablets containing excipients of similar and different deformation properties. The binary mixture tablets were prepared by direct compression using lactose, polyvinyl chloride (PVC), Eudragit RS 100, and microcrystalline cellulose (MCC). The application of percolation theory on the relationships between compactibility, P_max, or compression susceptibility (compressibility), γ, and mixture compositions reveals the presence of percolation thresholds even for mixtures of similar deformation properties. The results showed that all mixture compositions exhibited at least one discreet change in the slope, which was referred to as the percolation threshold. The PVC/Eudragit RS100 mixture compositions showed significant percolation threshold at 80% (w/w) PVC loading. Two percolation thresholds were observed from a series of binary mixtures containing similar plastic deformation materials (PVC/MCC). The percolation thresholds were determined at 20% (w/w) and 80% (w/w) PVC loading. These are areas where one of the components percolates throughout the system and the properties of the tablets are expected to experience a sudden change. Experimental results, however, showed that total disruption of the tablet physical properties at the specified percolation thresholds can be observed for PVC/lactose mixtures at 20–30% (w/w) loading while only minor changes in the tablets' strength for PVC/MCC or PVC/Eudragit RS 100 mixtures were observed.     

Comparison studies on the percolation thresholds of binary mixture tablets containing excipients of plastic/brittle and plastic/plastic deformation properties

Percolation theory has been used with great interest in understanding the design and characterization of dosage forms. In this study, work has been carried out to investigate the behavior of binary mixture tablets containing excipients of similar and different deformation properties. The binary mixture tablets were prepared by direct compression using lactose, polyvinyl chloride (PVC), Eudragit RS 100, and microcrystalline cellulose (MCC). The application of percolation theory on the relationships between compactibility, P_max, or compression susceptibility (compressibility), γ, and mixture compositions reveals the presence of percolation thresholds even for mixtures of similar deformation properties. The results showed that all mixture compositions exhibited at least one discreet change in the slope, which was referred to as the percolation threshold. The PVC/Eudragit RS100 mixture compositions showed significant percolation threshold at 80% (w/w) PVC loading. Two percolation thresholds were observed from a series of binary mixtures containing similar plastic deformation materials (PVC/MCC). The percolation thresholds were determined at 20% (w/w) and 80% (w/w) PVC loading. These are areas where one of the components percolates throughout the system and the properties of the tablets are expected to experience a sudden change. Experimental results, however, showed that total disruption of the tablet physical properties at the specified percolation thresholds can be observed for PVC/lactose mixtures at 20-30% (w/w) loading while only minor changes in the tablets' strength for PVC/MCC or PVC/Eudragit RS 100 mixtures were observed.     

A Comparison of Three Equilibrium Relative Humdity Measuring Devices

Three different types of equilibrium relative humidity measuring devices, capable of measuring the equilibrium relative humidity of a hygroscopic sample, were compared. The devices were: 1) a Container Hygrometer Apparatus, 2) a Dew Point Apparatus and 3) a Digital Hygrometer Apparatus. The devices were tested for accuracy of relative humidity measurement by generating atmospheres of known relative humidity in the sample compartments of the devices. The Digital Hygrometer Apparatus was found to be the device of choice for routine measurements, as it had acceptable accuracy over a wide range of humidites, and was easy-to-use. This device was used to measure the equilibrium relative humidity of a mixed-sugar tablet diluent at two different moisture contents. occur during compression, as indicated by the increase in drug release rate at lower porosities (see Figure 4).

Heckle developed a first-order relationship between pressure and porosity (12), which can sometimes be used to ascertain the mechanism of consolidation (13,14). Compression of formulations containing Avicel did not yield linear Heckle plots. Similar results were obtained by other investigators (15-17). Heckle plots for Emdex and Fast Flo Lactose were linear (see figure 3). Effect of microcapsule percentage

For each excipient there seemed to be a limit to the amount of microcapsules which could be incorporated into the formulation and still produce acceptable tablets. Avicel allowed incorporation of a greater percentage of microcapsules without serious degradation of tablet performance or microcapsule control over drug release. The apparent superiority of Avicel over Bndex or Fast Flo Lactose in protecting microcapsules from possible damage during compression may be attributed to Avieel's excellent cempressibi1i ty.     

Chitosan Matrix Tablets: The Influence of Excipients on Drug Release

The influence of excipients on drug release from chitosan matrix tablets was investigated, using diltiazem hydrochloride as model drug. Tablets were prepared by direct compression and the effect of different concentrations of the excipients lactose, sodium lauryl sulphate, sodium alginate, carbopol 934, citric acid and hydroxypropylmethyl-cellulose on drug release profiles was studied. Sustained release of the drug was obtained in all cases but the results indicate that both type and amount of excipient used influences drug release rate. The results support the idea that chitosan can be suitable as a basis for sustained release matrix tablets, and that drug release rate can be influenced by the addition of excipients. It is possible to make use of the interaction between chitosan and excipients in the formulation to provide further prolongation of release.     

Evaluation of Era-Tab as a Direct Compression Excipient

The physical and compressional properties of a modified rice starch, Era-Tab, were evaluated and compared with those of 4 commercially available direct compression excipients, namely, microcrystalline cellulose (Avicel PH-101), partially pregelatinized starch, spray-dried lactose (Super-Tab Lactose), and granular dicalcium phosphate dihydrate (Emcompress). It was found that Era-Tab possessed high flowability and adequate compressibility. The compacted material made with Era-Tab has a higher crushing strength and a lower friability than 3 other direct compression excipients, except microcrystalline cellulose. Tablets containing terfenadine of the same degree of hardness (10 kg) were also prepared using different direct compression excipients. The disintegration time of the tablets made with Era-Tab was approximately 2.5 min. The maximum of the accumulated percentage of terfenadine released from the tablet reached 90%, and 63.2% of it was released within 20 min. Both the powder characteristics and tablet properties show that the modified rice starch, Era-Tab, is a useful product as a direct compression tablet excipient.     

Chitosan Matrix Tablets: The Influence of Excipients on Drug Release

Abstract

The influence of excipients on drug release from chitosan matrix tablets was investigated, using diltiazem hydrochloride as model drug. Tablets were prepared by direct compression and the effect of different concentrations of the excipients lactose, sodium lauryl sulphate, sodium alginate, carbopol 934, citric acid and hydroxypropylmethyl-cellulose on drug release profiles was studied. Sustained release of the drug was obtained in all cases but the results indicate that both type and amount of excipient used influences drug release rate. The results support the idea that chitosan can be suitable as a basis for sustained release matrix tablets, and that drug release rate can be influenced by the addition of excipients. It is possible to make use of the interaction between chitosan and excipients in the formulation to provide further prolongation of release.     

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.     

Effect of Crospovidone on the Physical Properties of Acetaminophen Tablets

Acetaminophen tablets containing minimum amount of excipients and varying amounts of cross linked polyvinyl pyrrolidone were prepared under accurately controlled conditions of compression speed and pressure. The disintegration time, dissolution rate, crushing force, friability as well as effect of temperature and humidity on these parameters during storage were determined. Increasing proportions of the cross linked polymer (1-10%) did not influence crushing force or friability but significantly decreased disintegration and dissolution time. Satishctory tablets with desired properties were obtained by incorporation of optimum quantity of crospovidone. Storage of acetaminophen tablets at room temperature and humidity for a period of 4 weeks did not alter any of the physical properties tested weekly. However the combined effect of elevated temperature and humidity on tablet properties, especially on the dissolution time was significant. The influence of incorporation of equal amounts of crospovidone intragranularly and intra-plus extragranularly on the properties of granules and tablets were also evaluated with scaled-up formulations.     

EFFECT OF COMPRESSION AND DILUENT ON DRUG RELEASE FROM MASTIX MATRIX TABLETS. A STATISTICAL ANALYSIS

The effect of compression (30-150 kp/cm²) and diluent (PVP, lactose) on the in vitro release of PASNa from matrix tablets of mastix was evaluated on the basis of different mathematical models. The Higuchi and the exponential model were proved to be the best statistically. It seems that the use of lactose causes an increase on drug release. Also the relationship between the compression and the packing fraction of the tablets was examined. There seems to be a limit point above which no changes in packing fraction occure.