Authentication of artemether, artesunate and dihydroartemisinin antimalarial tablets using a simple colorimetric method.
The recent and widespread appearance of counterfeit antimalarial tablets in South-east Asia prompted the search for simple field assays to identify genuine drugs. In a recently described colorimetric assay for artesunate, Fast red TR salt reacted with an alkali-decomposition product of artesunate to produce a distinct yellow colour. However, that assay is specific for artesunate and it cannot be used to test for artemether. Because of potential concerns over artemether tablet counterfeiting, the colorimetric assay was modified to detect artemether, dihydroartemisinin and artesunate tablets. Other common antimalarials (artemisinin, chloroquine diphosphate, mefloquine HCl, sulphadoxine and pyrimethamine), as well as aspirin and acetaminophen, were negative in the assay, indicating its specificity for artemether, dihydroartemisinin and artesunate. The colorimetric method can be used to obtain a rapid visual assessment of tablet authenticity. The method can also be used to quantify the drug content of tablets, when used in conjunction with a spectrophotometer. (+info)
Guar gum as a carrier for colon specific delivery; influence of metronidazole and tinidazole on in vitro release of albendazole from guar gum matrix tablets.
PURPOSE: The present investigation is to study the influence of metronidazole and tinidazole on the usefulness of guar gum, a colon-specific drug carrier based on the metabolic activity of colonic bacteria, using matrix tablets of albendazole (containing 20% of guar gum) as a model formulation. METHODS: The matrix tablets of albendazole were subjected to in vitro drug release studies in simulated colonic fluids (4%w/v of rat caecal contents) obtained after oral treatment of rats for 7 days either with varying doses of metronidazole/ tinidazole and 1 mL of 2%w/v of guar gum or with 1 mL of 2%w/v of guar gum alone (control study) after completing the dissolution study in 0.1 M HCl (2 h) and pH 7.4 Sorensen's phosphate buffer (3 h). RESULTS: The guar gum matrix tablets of albendazole were found degraded by colonic bacteria of rat caecal contents and released about 44% of albendazole in simulated colonic fluids (control study) at the end of 24 h indicating the susceptibility of the guar gum formulations to the rat caecal contents. However, the release of albendazole decreased when the drug release studies were carried out in caecal contents of rats treated for 7 days with either metronidazole (10-50 mg/ kg once daily) or tinidazole (10-30 mg/ kg once daily), and the release of albendazole from the matrix tablets was found to be dose dependent. The release of the drug from guar gum formulations was found to increase with a decrease in the dose of metronidazole/tinidazole administered. The antimicrobial activity of metronidazole/ tinidazole against the anaerobic bacteria of the rat"s GI flora might have been inhibited to a varying degree depending on the dose of metronidazole/tinidazole administered. CONCLUSIONS: The results of the study showed that concomitant administration of either metronidazole or tinidazole with guar gum based colon-specific drug delivery systems may interfere with the targeting of drugs to colon. (+info)
Influence of the degree of polymerization on the behavior of cellulose during homogenization and extrusion/spheronization.
The study objective was to investigate the influence of the degree of polymerization (DP) of cellulose materials (microcrystalline cellulose [MCC] and powder cellulose [PC]) on the behavior of these materials during homogenization and extrusion/spheronization processes. Suspensions of the cellulose types with different DP values were homogenized using a high-pressure homogenizer. The particle size, agglomeration index, and apparent viscosity of these suspensions was determined at different times after pouring. Additionally, these different cellulose types were processed into pellets using the extrusion/spheronization method, and the water content and power consumption as a function of the DP were determined. Cellulose types with a high DP value showed greater particle size after homogenization than the types with a low DP value. In contrast, no relevant relationship between the apparent viscosity and DP could be observed. During the extrusion process, water content in the extrudate and pellet porosity were increased as the DP was increased for the extrudates produced at the same level of power consumption. MCC types with various DPs compared with PC provided a novel way of understanding the role of cellulose in the extrusion process. The DP showed a remarkable influence on the physicochemical properties of the cellulose materials and, consequently, on the behavior of these materials during the extrusion/spheronization process. It is postulated that the sponge model is more appropriate for the cellulose type with high DP (PC), whereas the gel model is more applicable to cellulose types with lower DP (MCC). (+info)
Direct pelletization in a rotary processor controlled by torque measurements. II: effects of changes in the content of microcrystalline cellulose.
In the present study we investigated the effect of changes in the content of microcrystalline cellulose (MCC) on a direct pelletization process in a rotary processor in which the liquid addition was terminated once a certain increase in torque was produced. Nine different mixtures of MCC and lactose with MCC contents varying from 10% to 100% (w/w) were pelletized using 6 different torque increase levels, and the changes in pellet characteristics were investigated. The pellet characteristics investigated were pellet shape, size, and size distribution as well as the water content of the pellets at the end of liquid addition. To produce spherical agglomerates with suitable characteristics in a reproducible way, a content of at least 20% (w/w) MCC was found necessary. Linear correlations were found between the MCC content and the water content and between the torque increase and the water content, showing that the torque increase is suitable to control the process. A higher torque increase or a higher MCC content was found to increase the water content independently of each other. (+info)
Estimation of capping incidence by indentation fracture tests.
The purpose of this study was to predict the capping tendencies of pharmaceutical powders by creating indentation fracture on compacts. Three sets of binary mixtures containing different concentrations of each ingredient were used in the study. The binary mixtures were chosen to represent plastic-plastic, plastic-brittle, and brittle-brittle combination of materials. The mixtures were tableted at different pressures and speeds on Prester, a tablet press simulator. These mixtures were also compacted on the Instron Universal Testing Machine 4502. Static indentation tests were done on these compacts at different depths until surface cracking and chipping were observed. The extent of surface cracking and chipping was observed from light microscope and scanning electron microscope images. A rank order correlation was observed between lamination susceptibility and the depth at which indentation failure occurred. It was concluded that indentation fracture tests could provide a useful estimate of lamination properties of pharmaceutical powders. (+info)
Study of crystallization of endogenous surfactant in Eudragit NE30D-free films and its influence on drug-release properties of controlled-release diphenhydramine HCl pellets coated with Eudragit NE30D.
This study investigates the crystallization of the endogenous surfactant nonoxynol 100 in Eudragit NE30D-free films during storage and the influences of nonoxynol 100 on the dissolution of diphenhydramine hydrochloric acid (HCl) pellets coated with Eudragit NE30D before and after aging at ambient conditions. Polarizing light microscopy showed that when Eudragit NE30D-free films were stored at ambient conditions, off-white, flower-shaped crystals formed and increased in the polymer film as storage time increased. Also, x-ray diffraction showed polymer crystals in the aged free film. Thermogravimetric analysis showed no evidence of combined volatile molecules with the polymer molecules, and Fourier transformed infrared spectroscopy (FTIR) data suggested the same chemical composition of the polymer before and after phase separation. Further, from normal light microscopy, the appearance of the melting droplets in the polymer film indicated that the polymer molecules did not form the crystals. After the extraction of nonoxynol 100 by water, the free film formed by the water-extracted Eudragit NE30D was found free of the crystals after aging at the same conditions. The combination of the thermogravimetric analysis, FTIR, and microscopy showed that the origin of the crystals in dry Eudragit NE30D-free films came from nonoxynol 100, and not from the polymer molecules themselves. Monitoring by differential scanning calorimeter, it was found that the rates of crystallization of nonoxynol 100 were faster when the films were stored at 30 degrees C and 40 degrees C than when stored at ambient conditions and 45 degrees C. When stored at -5 degrees C, the crystallization rate was nearly zero. As the temperature got closer to melting temperature, the crystallization rate was very low because the system was in a thermodynamically disfavored state. The rate gradually increased and finally passed through a maximum as the crystallization temperature decreased. As the temperature kept decreasing, the crystallization rate became small again and eventually stopped because the system turned into a kinetically disfavored state. Because the phase transition of nonoxynol 100 in Eudragit NE30D occurred at ambient conditions, its influence on the dissolution of diphenhydramine HCl pellets coated with Eudragit NE30D was studied. Three different levels of nonoxynol 100 were used in Eudragit NE30D dispersions to make 3 different batches of Eudragit NE30D film-coated, controlled-release diphenhydramine HCl pellets. The results showed the dissolution rate increased as the level of nonoxynol 100 increased in the coating formula. Compared to the commonly used water-soluble additive human peripheral mononuclear cell, nonoxynol 100 was more effective in enhancing the dissolution of diphenhydramine HCl from pellets coated with Eudragit NE30D. Further study showed that the phase separation of the surfactant during aging tends to stabilize or slightly increase dissolution rates at higher surfactant levels. (+info)
Comparative evaluation of tableting compression behaviors by methods of internal and external lubricant addition: inhibition of enzymatic activity of trypsin preparation by using external lubricant addition during the tableting compression process.
This study evaluated tableting compression by using internal and external lubricant addition. The effect of lubricant addition on the enzymatic activity of trypsin, which was used as a model drug during the tableting compression process, was also investigated. The powder mixture (2% crystalline trypsin, 58% crystalline lactose, and 40% microcrystalline cellulose) was kneaded with 5% hydroxypropyl cellulose aqueous solution and then granulated using an extruding granulator equipped with a 0.5-mm mesh screen at 20 rpm. After drying, the sample granules were passed through a 10-mesh screen (1680 microm). A 200-mg sample was compressed by using 8-mm punches and dies at 49, 98, 196, or 388 MPa (Mega Pascal) at a speed of 25 mm/min. The external lubricant compression was performed using granules without lubricant in the punches and dies. The granules were already dry coated by the lubricant. In contrast, the internal lubricant compression was performed using sample granules (without dry coating) containing 0.5% lubricant. At 98 MPa, for example, the compression level using the external lubricant addition method was about 13% higher than that for internal addition. The significantly higher compressing energy was also observed at other MPas. By comparison, the friction energy for the external addition method calculated based on upper and lower compression forces was only slightly larger. The hardness of tablets prepared using the internal addition method was 34% to 48% lower than that for the external addition method. The total pore volume of the tablet prepared using the external addition method was significantly higher. The maximum ejection pressure using the no-addition method (ie, the tablet was prepared using neither dry-coated granules nor added lubricant) was significantly higher than that of other addition methods. The order was as follows: no addition, external addition, and then internal addition. The ejection energy (EE) for internal addition was the lowest; for no addition, EE was the highest. In the dissolution test, the tablets obtained using external addition immediately disintegrated and showed faster drug release than those prepared using internal addition. This result occurred because the water penetration rate of the tablet using the external addition was much higher. The trypsin activity in tablets prepared using the external addition method was significantly higher than that produced using the internal addition method at the same pressure. All these results suggest that the external addition method might produce a fast-dissolution tablet. Because the drug will be compressed using low pressure only, an unstable bulk drug may be tableted without losing potency. (+info)
Influence of drug release properties of conventional solid dosage forms on the systemic exposure of highly soluble drugs.
This study was designed to theoretically investigate the influence of drug release properties, characterized by the disintegration of a solid dosage form and dissolution of drug particles, on the systemic exposure of highly soluble drugs in immediate release products. An absorption model was developed by considering disintegration of a solid dosage form, dissolution of drug particles, gastrointestinal transit flow, and intestinal absorption processes. The absorption model was linked to a conventional pharmacokinetic model to evaluate the effect of disintegration and dissolution on the peak exposure (Cmax) and total exposure of area under the curve (AUC). Numerical methods were used to solve the model equations. The simulations show that the effect of disintegration of a dosage form and dissolution of drug particles depend on the permeability of a drug, with a low-permeability drug having a greater effect. To provide similar exposure to an oral solution formulation, a solid dosage form containing a low-permeability drug would need to dissolve more rapidly than a solid dosage form containing a high-permeability drug. It was shown theoretically for poorly permeable drugs that the disintegration rate constant has to be greater than 9 hour(-1)(equivalent to approximately 90% in 30 minutes) to make both AUC and Cmax ratios higher than.9, ensuring the confidence interval of.80 to 1.25. The rapid in vitro release requirement of at least 85% dissolved in 30 minutes is sufficient for highly soluble and highly permeable drugs. However, for highly soluble and poorly permeable drugs, the appropriate in vitro release requirement seems to be 90% dissolved in 30 minutes. (+info)