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At least 37 records · Page 2Linked to original sources

PubMed2004

Modeling of adhesion in tablet compression. II. Compaction studies using a compaction simulator and an instrumented tablet press.

Adhesion problems are usually not identified until prolonged compression runs are studied near the end of the drug development process. During tablet manufacturing, adhesion problems encountered are usually addressed by statistically designed experiments based on experience. It would be a significant benefit for the pharmaceutical industry if adhesion problems could be identified early in drug development based on molecular considerations of the drug substance and/or prototype formulations. Drug substance-punch face interactions were reported in the first of the articles in this series, and focused on the elucidation of adhesion problems in tablet compression. It was hypothesized that the intermolecular interactions between drug molecules and the punch face was the first step (or criterion) in the adhesion process, and that the rank order of adhesion during tablet compression should correspond with the rank order of these energies of interaction. That is, the interaction between the molecular structure of the drug and the metal surface determines the primary interaction event or relative potential for adhesion, while the mechanical processes and/or lubrication effects may subsequently impact the extent of adhesion. Molecular simulations and atomic force microscopy were used to establish the rank order of the work of adhesion of a series of profen compounds. The results predicted that the relative degree of drug substance-punch face adhesion should decrease in the order of ketoprofen > ibuprofen > flurbiprofen. In this study, the authors investigated whether the rank order of the work of adhesion established on the molecular level and interparticulate level holds true in the tableting environment by measuring tablet take-off force, ejection force, and visual observation of the punch surfaces for both pure drug compacts and formulated tablets. The compaction simulator was used for pure profen compacts, while the instrumented tablet press for formulated tablets. Due to the inability to extract the adhesion force component from the total ejection force measurement, tablet ejection force was not used as a criterion to judge the adhesion behavior of the model compounds. The criteria used for judgement of punch face adhesion were tablet take-off force and visual observation of the punch faces. The rank order of adhesion for both pure drug and formulated tablets was determined to follow the order of ketoprofen > ibuprofen > flurbiprofen. The effect of run time on adhesion behavior was also investigated. Therefore, the rank order of the punch-face adhesion tendencies for the series of profen compounds was determined, and found to agree with the data from the predictive methods reported in the first article.

Adhesiveness↗

PubMed2001

Assessing tablet bond types from structural features that affect tablet tensile strength.

PURPOSE: The aim of this article was to study the possibility of assessing the structural features affecting tablet tensile strength to obtain information on the dominating bond types, i.e. interparticulate attractions, in tablets. METHODS: The features of the internal tablet structure considered to be important for tablet tensile strength were assessed using a simple tablet model for tablets made from seven materials: potassium chloride, sodium chloride, sodium bicarbonate, lactose, sucrose, microcrystalline cellulose, and ascorbic acid. RESULTS: Tablet porosity and particle size (measured as external specific surface area by permeametry) were the structural features that best correlated with tablet tensile strength. These features were described by a "structural factor," which was combined with tablet tensile strength, as an "interaction factor," to reflect the dominating bond types in tablets. CONCLUSION: The qualitative results gave dominating bond types in the tablets studied that matched the results of earlier studies, thus supporting the applicability of the method.

Models, Chemical↗

PubMed2002

Investigation of the effect of tablet surface area/volume on drug release from hydroxypropylmethylcellulose controlled-release matrix tablets.

The purpose of this study was to investigate the influence of tablet surface area/volume (SA/Vol) on drug release from controlled-release matrix tablets containing hydroxypropylmethylcellulose (HPMC). Soluble drugs (promethazine HCl, diphenhydramine HCl, and propranolol HCl) were utilized in this study to give predominantly diffusion-controlled release. Drug release from HPMC matrix tablets with similar values of SA/Vol was comparable within the same tablet shape (i.e., flat-faced round tablets) and among different shapes (i.e., oval, round concave, flat-faced beveled-edge, and flat-faced round tablets). Tablets having the same surface area but different SA/Vol values did not result in similar drug release; tablets with larger SA/Vol values hadfaster release profiles. Utility of SA/Vol to affect drug release was demonstrated by changing drug doses, and altering tablet shape to adjust SA/Vol. When SA/Vol was held constant, similar release profiles were obtained with f2 metric values greater than 70. Thus, surface area/volume is one of the key variables in controlling drug release from HPMC matrix tablets. Proper use of this variable has practical application by formulators who may need to duplicate drug release profiles from tablets of different sizes and different shapes.

Delayed-Action Preparations↗

PubMed2003

Hydroxypropyl methylcellulose based cephalexin extended release tablets: influence of tablet formulation, hardness and storage on in vitro release kinetics.

The object of this study was to develop hydroxypropyl methylcellulose (HPMC) based cephalexin extended release tablet, which can release the drug for six hours in predetermined rate. Twenty-one batches of cephalexin tablets were prepared by changing various physical and chemical parameters, in order to get required theoretical release profile. The influences of HPMC, microcrystalline cellulose powder (MCCP), granulation technique, wetting agent and tablet hardness on cephalexin release from HPMC based extended release tablets were studied. The formulated tablets were also characterized by physical and chemical parameters. The dissolution results showed that a higher amount of HPMC in tablet composition resulted in reduced drug release. Addition of MCCP resulted in faster drug release. Tablets prepared by dry granulation was released the drug slowly than the same prepared with a wet granulation technique. Addition of wetting agent in the tablets prepared with dry granulation technique showed slower release. An increase in tablet hardness resulted in faster drug release. Tablets prepared with a wet granulation technique and having a composition of 9.3% w/w HPMC with a hardness of 10-12 kg/cm(2) gave predicted release for 6 h. The in vitro release data was well fit in to Higuchi and Korsmeyer-Peppas model. Physical and chemical parameters of all formulated tablets were within acceptable limits. One batch among formulated twenty-one batches was successful and showed required theoretical release. The effect of storage on in vitro release and physicochemical parameters of successful batch was studied and was found to be in acceptable limits.

Cephalexin↗

PubMed1989

The United States experience with oral controlled-release morphine (MS Contin tablets). Parts I and II. Review of nine dose titration studies and clinical pharmacology of 15-mg, 30-mg, 60-mg, and 100-mg tablet strengths in normal subjects.

The results of nine US multicenter, sequential crossover, dose titration studies of controlled-release oral morphine (MS Contin 30 mg tablets [MSC], Purdue Frederick, Norwalk, CT) are reviewed in Part I. The studies demonstrated the prolonged analgesic efficacy of the preparation in the treatment of patients with moderate to severe cancer-related pain. Approximately 93% of the patients achieved satisfactory to excellent analgesia on a 12-hour regimen when appropriate dose titration was allowed. The remaining patients were successfully maintained on an 8-hour regimen. The preparation was well-tolerated and comparable in safety to immediate-release oral morphine. In global evaluations, MSC was judged to be significantly (P less than 0.05) more effective, and with significantly (P less than 0.05) fewer side effects than both the prestudy opioid analgesics and 4-hour immediate-release oral morphine. Patients had a broad range of morphine requirements (mean daily MSC dose, 240 mg; range, 60 mg/day to 1800 mg/day); therefore various MSC tablet strengths were developed. Part II presents three studies in which the MSC formulations (15-mg, 60-mg, and 100-mg tablets) were compared to the 30-mg tablet within three randomized, single-dose, two-way crossover, analytically blinded bioavailability protocols, to determine bioequivalence and dose proportionality. The maximum morphine concentration, time of maximum morphine concentration, and area under the plasma morphine versus 12-hour and 24-hour time curve (AUC 0.12; AUC 0.24) were determined in each study. There were no significant differences between the values associated with MSC 1 X 30 mg tablet and 2 X 15 mg tablets (study 1), MSC 2 X 30 mg tablets and 1 X 60 mg tablet (study 2), and MSC 3 X 30 mg tablets and 1 X 100 mg tablet (study 3, values adjusted to dose of 90 mg), except for one marginally significant difference in study 3 (AUC 0.24; P = 0.04) which was not clinically or biopharmaceutically significant. The results showed that MSC 15-mg, 30-mg, 60-mg, and 100-mg dosage strengths are bioequivalent and dose proportional, and, therefore, therapeutically interchangeable. It was concluded that with routine assessment of the patient and adherence to the principles of analgesic dosing, MSC can be successfully used to control cancer-related pain. Furthermore, the availability of various MSC tablet strengths can be expected to facilitate the analgesic management of a patient population with widely differing opioid requirements.

Administration, Oral↗

PubMed2002

A double-blind, single-dose comparison of the analgesic efficacy of tramadol/acetaminophen combination tablets, hydrocodone/acetaminophen combination tablets, and placebo after oral surgery.

BACKGROUND: Improved clinical outcomes have been documented with combinations of oral analgesic agents, particularly those with complementary activities. However, because not all combinations or dose ratios lead to enhanced analgesia or reduced adverse events (AEs), each combination and dose ratio must be evaluated individually in carefully designed preclinical and clinical trials. OBJECTIVE: The goal of the study was to compare the efficacy and safety of 37.5 mg tramadol/325 mg acetaminophen tablets (T/APAP), 10 mg hydrocodone bitartrate/650 mg acetaminophen tablets (HC/APAP), and placebo in the treatment of postoperative dental pain. METHODS: This was a single-center, double-blind, parallel-group, placebo- and active-controlled study in adults with at least moderate pain (score > or =50 on a 100-mm pain visual analog scale) after extraction of > or =2 impacted third molars. Patients were randomized to receive 1 or 2 T/APAP tablets, 1 HC/APAP tablet, or placebo. Scores for hourly pain relief (PAR), pain intensity difference (PID), and combined PAR and PID (PRID) were based on reported pain at 30 minutes and each successive hour for 8 hours. Primary efficacy measures were summary pain intensity and pain relief scores (total pain relief [TOTPAR], sum of pain intensity differences [SPID], and sum of pain relief and pain intensity differences [SPRIDI) for 0 to 4 hours, 4 to 8 hours, and 0 to 8 hours. Secondary efficacy measures were hourly PAR, PID, and PRID scores; onset and duration of pain relief; time to remedication with a supplemental analgesic agent; and patients' overall assessment of medication. RESULTS: Two hundred adults took part in the study (50 per treatment group) and were included in the efficacy and safety analyses. T/APAP 75/650 mg and HC/APAP were statistically superior to placebo on the primary efficacy measures of TOTPAR, SPID, and SPRID (P < or = 0.024), as well as on hourly PAR, PID, and PRID over 6 hours (P < or = 0.045). All active treatments were statistically superior to placebo in terms of onset of pain relief (P < or = 0.001), duration of pain relief (P < or = 0.024), time to remedication (P < 0.001), and patients' overall assessment of medication (P < 0.001). A statistically significant dose response with T/APAP (2 tablets > 1 tablet > placebo) was seen for TOTPAR, SPID, and SPRID (all, P < or = 0.018). The median time to onset of pain relief was approximately 34.0 minutes with 2 T/APAP tablets and 25.4 minutes with HC/APAP. Although the median time to onset of pain relief was shorter with HC/APAP, two T/APAP tablets had comparable efficacy to HC/APAP. The median time to remedication with a supplemental analgesic agent was 169.0 minutes in the T/APAP 75/650 mg group and 204.0 minutes in the HC/APAP group. However, the duration of pain relief, as defined by time to remedication, was not significantly different between these 2 groups. The overall incidence of AEs was lower with T/APAP (0% treatment-related AEs) than with HC/APAP (4%) or placebo (10%). The incidence of nausea (18% T/APAP, 36% HC/APAP) and vomiting (12% T/APAP, 30% HC/APAP) was approximately 50% lower with 2 T/APAP tablets than with HC/APAP (P < 0.05). CONCLUSIONS: T/APAP tablets provided effective, rapid (< or = 34 minutes), dose-dependent analgesia for the treatment of postoperative dental pain. Two T/APAP tablets provided analgesia comparable to that provided by HC/APAP with better tolerability.

Acetaminophen↗

PubMed2004

Development and evaluation of the tablets coated with the novel formulation termed thin-layer sugarless coated tablets.

The purpose of this study was to develop and evaluate the thin-layer sugarless coated tablets containing Vitamin C, Vitamin E, Vitamin B2, calcium pantothenate, and L-cysteine. As a result of the formulation study, three coating layers, 2% under coating (UC), 38% build-up coating (BC), and 5% syrup coating (SC) were necessary for sufficient impact toughness, elegant appearance, and improvement of appearance stability after storage at 25 degrees C/75% RH for 6 months under open conditions. We demonstrated that the thin-layer sugarless coated tablets are superior to the sugar-coated tablets in terms of small tablet size and stability of calcium pantothenate. It was due to the coating method, the continuous spray mist method, which can minimize the thicknesses of coating layers and the moisture content in the tablets. We also demonstrated that the thin-layer sugarless coated tablets are superior to the film-coated tablets in terms of masking ability of the unpleasant odor and the appearance, stability of the appearance, and low hygroscopicity. It was due to the dense, opaque, and stable coating layers mainly consist of erythritol. We revealed that thin-layer sugarless coated tablets have both advantages of film-coated tablets and sugar-coated tablets.

Dietary Supplements↗

PubMed2004

Evaluation of novel one-step dry-coated tablets as a platform for delayed-release tablets.

Using a novel one-step dry-coated tablets (OSDRC) manufacturing method, which we have recently invented, we evaluated the possibility of its application to delayed-release tablets. The manufacturing method for OSDRC is different from conventional methods in that dry-coated tablets can be made with only one process. One of the major advantages of OSDRC is that we can expect to produce tablets, which always contain the core exactly in the center of the whole tablet. This characteristic means that the thickness of outer layer is constantly uniform, which is difficult to achieve with the conventional dry-coated tablets. The effects of different outer layer thicknesses and various compression pressures were examined using HPMC to evaluate OSDRC applicability to delayed-release tablets. We proved that the lag-time can be adjusted only by changing the thickness of the outer layer without any arrangement of its ingredients, which is quite different from the conventional approach. Further, the lag-time of each OSDRC prepared in the 100-200 MPa compression pressure range was almost the same, indicating the lag-time of OSDRC under these compression pressures does not vary. The release rate of the drug (acetaminophen) from the OSDRC with 0.5 and 1.0 mm outer layer thicknesses was almost constant independent of compression pressure. On the other hand, the release rate of the OSDRC with a 2.0 mm outer layer thickness was delayed compared to that of other thicknesses. That is, in the tablets with 2.0 mm outer layer thickness, the release rate declined since its outer layer thickness was sufficient to form a gel-layer. In conclusion, OSDRC could be a platform for delayed-release tablets, which do not utilize the conventional method used for dry-coated tablets.

Acetaminophen↗

PubMed2000

A five way crossover human volunteer study to compare the pharmacokinetics of paracetamol following oral administration of two commercially available paracetamol tablets and three development tablets containing paracetamol in combination with sodium bicarbonate or calcium carbonate.

This report concerns a single dose randomized five way crossover study to compare the pharmacokinetics of paracetamol from two commercially available paracetamol (500 mg) tablets and three different development paracetamol (500 mg) tablet formulations containing either sodium bicarbonate (400 mg), sodium bicarbonate (630 mg) or calcium carbonate (375 mg). The results demonstrated that addition of sodium bicarbonate (630 mg) to paracetamol tablets, increased the rate of absorption of paracetamol relative to conventional paracetamol tablets and soluble paracetamol tablets. Addition of sodium bicarbonate (400 mg) to paracetamol tablets increased the absorption rate of paracetamol relative to conventional paracetamol tablets, but there was no difference in the rate of absorption compared to soluble paracetamol tablets. Inclusion of calcium carbonate (375 mg) to paracetamol tablets had no effect on absorption kinetics compared to the conventional paracetamol tablet. The faster absorption observed for the sodium bicarbonate formulations may be as a result of an increase in gastric emptying rate leading to faster transport of paracetamol to the small intestine where absorption takes place.

Acetaminophen↗

PubMed2002

A randomised, double-blind, double-dummy comparison of the efficacy and tolerability of lercanidipine tablets and losartan tablets in patients with mild to moderate essential hypertension.

A double-blind, double-dummy, randomised, multicentre study to compare the efficacy and tolerability of lercanidipine with losartan. Patients with mild to moderate hypertension (supine diastolic blood pressure (DBP) 95-115 mm Hg) were enrolled and underwent a placebo run-in period of 14-30 days before random allocation to lercanidipine tablets 10 mg once-daily (n = 234) or losartan tablets 50 mg once-daily (n = 231) during the assessment period (approximately 16 weeks). Titration to lercanidipine 20 mg once-daily (two 10 mg tablets) or losartan 100 mg once-daily (two 50 mg tablets) was allowed after 8 weeks, if necessary. At the end of the study, 71% of patients who received lercanidipine tablets had achieved normalised DBP (ie, < or =90 mm Hg) and 81% had responded to treatment (ie, DBP < or =90 mm Hg or a decrease in DBP > or =10 mm Hg). The corresponding numbers in the losartan tablets group were 65% and 78%, respectively. In those patients who required dose titration, there was evidence of a greater response with lercanidipine tablets than with losartan tablets. Both treatments were well tolerated with a low incidence of adverse drug reactions and a low withdrawal rate. In conclusion, the antihypertensive effects of lercanidipine tablets were comparable with those of losartan tablets; both treatments gave a high response rate for an antihypertensive monotherapy and were very well tolerated.

Adolescent↗

PubMed2005

Coprocessing of powdered cellulose and magnesium carbonate: direct tableting versus tableting after roll compaction/dry granulation.

Mixtures of magnesium carbonate (MC) with three types of powdered cellulose (M80, P290, A300) were tableted directly or after roll compaction/dry granulation. The fraction of powdered cellulose in the mixture was varied from 0% to 25% (w/w). The properties of the granules, blends, and their corresponding tablets were analyzed. Granules with a low amount of A300 showed the best flow properties, whereas the fibrous shape of the binding agents M80 and P290 impaired the free flow. Heckel plots showed clearly the different behavior of powdered cellulose in blends and granules during the tableting process. The Heckel-Plots for pure MC powder and granulated MC (MCgr) were similar. Increasing the fraction of powdered cellulose resulted in a fan-shaped set of curves, which is a reflection of an increased densification. Physical mixtures of all three powdered celluloses and granulated mixtures of M80 resulted in a higher densification compared with pure MC. In contrast, the granulated mixtures of P290 and A300 resulted in a diminished densification during tableting, which means that the coprocessed mixtures behaved differently during tableting compared with the physical mixtures. The curves were lower than those of pure MC and MCgr most pronounced at a fraction of 5% powdered cellulose. The tablet pore structure was evaluated by mercury porosimetry. The addition of P290 and A300 to the dry granules resulted in tablets with a higher fraction of smaller pores. Comparably high values for tablet tensile strength and low friability resulted from this special tablet structure. Roll compacted/dry granulated MC, coprocessed with 5% of P290 or A300, seems to be a promising excipient for direct compression. This coprocessed product combines good flow and tablet properties, and is superior to pure MC or a physical mixture of MC and PC.

Cellulose↗

PubMed2001

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.

Algorithms↗

PubMed2005

Effect of tablet geometrical structure on the dehydration of creatine monohydrate tablets, and their pharmaceutical properties.

The effects of compression and pulverization on the dehydration kinetics and hardness of creatine monohydrate tablets were studied using a variety of kinetic equations and physical models. The dehydration behavior of unpulverized and pulverized tablets was investigated by using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The hardness of both unpulverized and pulverized monohydrate tablets was significantly decreased after dehydration. The relationship between the degree of dehydration and the tablet hardness of both unpulverized and pulverized monohydrate tablets formed a straight line. The results suggest that the reduction in tablet hardness is dependent on the dehydration of crystal water, and the values of the slopes indicate that the bonding energy of the unpulverized sample was stronger than that of the pulverized sample. The dehydration kinetics of the unpulverized and pulverized monohydrate tablets were evaluated by analyzing the fit of the isothermal DSC data using a variety of solid-state kinetic models. The dehydration of the unpulverized tablets at various levels of compression pressure followed the 3-dimensional growth of nuclei mechanism. In contrast, although the dehydration kinetics of pulverized monohydrate tablets compressed at 500 and 750 kg/cm2 followed the 3-dimensional diffusion mechanism, those compressed at 1000 kg/cm2 followed the 3-dimensional growth of nuclei mechanism. The PXRD analysis indicated that the diffraction intensity of the pulverized monohydrate powder was significantly lower than that of the unpulverized powder. The diffraction peaks of the (h00) planes and the micropore structure of the unpulverized monohydrate tablets were affected by pulverization and compression force, respectively.

Compressive Strength↗

PubMed2002

The effect of tablet formulation and hardness on in vitro release of cephalexin from Eudragit L100 based extended release tablets.

Eighteen batches of cephalexin extended release tablet were prepared by wet granulation method by using Eudragit L100. The effect of the concentration of Eudragit L100, microcrystalline cellulose and tablet hardness on cephalexin release was studied. The formulated tablets were also characterized for physical and chemical parameters. The dissolution results showed that a higher amount of Eudragit in tablet composition and higher tablet hardness resulted in reduced drug release. An increased amount of microcrystalline cellulose in tablet composition resulted in enhanced drug release. Tablet composition of 13.3% w/w Eudragit L100 and 6.6 to 8% w/w microcrystalline cellulose with hardness of 7-11 kg/cm2 gave predicted release for 6 h. The in vitro release was compared with a marketed tablet. Physical and chemical parameters of all formulated tablets were within acceptable limits. The effect of storage on in vitro release and physicochemical parameters of tablets was evaluated and two batches among formulated eighteen batches found to be in acceptable limits.

Cephalexin↗

PubMed1997

[Clinical efficacy of GG032X tablets, a new dosage form of ondansetron (fast dispersing tablet), on cisplatin-induced nausea and emesis].

The inhibitory effects of GG032X tablets, a new dosage form (fast dispersing tablet) of ondansetron, 5-HT2 receptor antagonist, on nausea and emesis induced by cisplatin (CDDP), were investigated along with safety and usefulness. Subjects were chemotherapy patients starting CDDP administration for the first time, who were receiving a high single dose of CDDP (50 mg/m2 or more and intravenous drip infusion of less than 4 hours), or lower multiple doses of CDDP (a single dose of 10 mg/m2 or more, administered intravenously for 3-5 consecutive days). GG032X tablets were administered orally 1-2 hours before CDDP administration. In lower multiple doses of CDDP, GG032X tablets and CDDP were administered, as much as possible, at the same respective time when they were administered on the first day. Efficacy of GG032X tablets was evaluated in terms of inhibitory effect on nausea and emesis 24 hours after administration of a high single dose of CDDP, and of the inhibitory effect on nausea and emesis during the study period (3-5 days) in lower multiple doses of CDDP. Efficacy, safety and usefulness were evaluated in accordance with the evaluation criteria used in the clinical study of already-approved ondanstron tablets. In a high single dose of CDDP, the cases judged "effective" or better in the investigation of the inhibitory effect of the drug on nausea and emesis, accounted for 52.9% (63/119 cases). As for the overall safety rating, the cases judged as "safe" accounted for 87.0% (107/123 cases), and as a "minor safety problem" accounted for 13.0% (16/123 cases). As for the usefulness rating, the cases judged "useful" or better accounted for 52.1% (62/119 cases). Major adverse effects included headache, fever, atrial fibrillation and increases in total bilirubin, GOT and GPT values. None of these was serious, and the patients recovered without any treatment or by nosotropic therapy. Meanwhile, in lower multiple doses of CDDP, the inhibitory effect judged "effective" or better accounted for 70.6% (12/17 cases). As for the overall safety rating, all cases were judged "safe". In terms of usefulness, those cases judged "useful" or better accounted for 70.6% (12/17 cases). No adverse effect was observed. Study results of these two groups were almost the same as those for already-approved ondansetron tablets. According to the results of questionnaires for the patients who participated in the study and took GG032X tablets, the drug was found to be easy to take and had favorable results. Based on the above results, GG032X tablets were evaluated as having the same inhibitory effect as the already-approved ondansetron tablets against CDDP-induced nausea and emesis, and were considered safe and clinically useful.

Administration, Oral↗

PubMed2001

Bioequivalence study of a novel Solutab tablet formulation of amoxicillin/clavulanic acid versus the originator film-coated tablet.

With amoxicillin/clavulanic acid Solutab tablet, a new tablet formulation of amoxicillin/clavulanic acid (500/125), was developed. The aim of the present study was to demonstrate bioequivalence between the new tablet formulation, taken as an intact tablet and after prior dispersal, versus the originator product viz. Augmentan film-coated tablet. The study was performed in 48 healthy volunteers, according to an open, single-dose three-period, crossover design. Blood samples were taken prior to each administration and at 10 time points after dosing. Plasma concentrations of amoxicillin and clavulanic acid were determined by validated high performance liquid chromatography with UV detection. With regard to amoxicillin, the results were within the preset bioequivalence range of 0.8 to 1.25 for the ratios of the primary parameters AUC(0-t) and Cmax. In terms of clavulanic acid the 90% confidence intervals of the ratios for AUC(0-t) and Cmax versus the reference lay outside the predefined bioequivalence range of 0.75 to 1.33. This result, however, was mainly due to the large variability of the reference formulation compared to the amoxicillin/clavulanic acid Solutab tablet. Based on statistical indications that 3/48 subjects with extremely low levels on the reference formulation could be regarded as "outliers" and after excluding these subjects' data from the statistical analysis, results for clavulanic acid were within the predefined bioequivalence range of 0.75 to 1.33. Overall, the amoxicillin/clavulanic acid Solutab tablet provided, in comparison to the reference tablet, less variable levels of clavulanic acid, thus giving more appropriate protection to the available amoxicillin. Thirteen adverse events were reported post dosing by 7 subjects. There were no differences in incidence of adverse events between amoxicillin/clavulanic acid Solutab tablet taken intact or dispersed and Augmentan.

Adolescent↗

PubMed1980

Preparation of enteric-coated microcapsules for tableting by spray-drying technique and in vitro simulation of drug release from the tablet in GI tract.

Improved methods were developed for the preparation of enteric-coated microcapsules for tableting by a spray-drying technique, and the drug release behavior from the tableted microcapsules was investigated using a disintegration apparatus and a new in vitro method of simulating the GI tract. As a model system, ammonium solutions of sulfamethoxazole and cellulose acetate phthalate were spray dried using a centrifugal wheel atomizer at 140 degrees. Additives such as colloidal silica, montmorillonite clay, and talc were included in the formulations for spray drying. The influence of the additives on the particle diameter, density, packing properties, and compressibility of the product and on the release characteristics of the resultant tablet in vitro were investigated. The additives in the formulations greatly improved the flow properties of the spray-dried products, which could be tableted easily. Products from the nonadditive formulations could not be tableted due to their poor flowability. The hardness and disintegration rate of the tablet increased with increasing concentration of additives in the formulations. X-ray analysis and IR spectroscopy confirmed that the crystals of sulfamethoxazole in the spray-dried microcapsules with cellulose acetate phthalate were converted from Form I to Form II. In vitro release characteristics of the tablets were studied using a disintegrator (JP) in buffer solutions (pH 1.2 and 7.5) and distilled water. Enteric action of the spray-dried products was proved by comparison with the original nontreated powders. The additives in the tablet increased the release rate at the initial stage in all dissolution media used. A new in vitro release simulator was devised consisting of a flow-type dissolution container in which the pH of the medium was changed continuously from 1.2 to 7.0 to simulate the pH change of tablets exposed to the GI tract.

Chemical Phenomena↗

PubMed2006

Liquid boundary movements in cylindrical and convex hydrophobic matrix tablets: Effects on tablet cracking and drug release.

The aim of this study was to investigate liquid penetration into both cylindrical and convex hydrophobic matrix tablets and to relate the changes in tablet structure to drug release. Starch acetate with degree of substitution of 2.7 was used as a hydrophobic matrix former and anhydrous caffeine as a freely soluble model drug. Phenolred was used as a colouring agent to enhance the visual detection of the liquid boundary movements, which were examined in axial and radial directions for both types of tablets. The tablets started to expand during the dissolution, resulting in cracking as the liquid boundary penetrated into tablet. The cracking influences drug release by shortening the diffusion path and decreasing the tortuosity. The liquid boundaries proceed differently in cylindrical and convex tablets, this being attributable to differences in pore structure and density distribution. Cylindrical tablets are quite homogeneous in terms of density, but convex tablets have more porous areas at the domes of the tablet.

Algorithms↗