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Enamel biopsy results of children receiving fluoride tablets.

This study measured the fluoride in tooth enamel of 338 schoolchildren after daily use of acidulated phosphate-fluoride (APF) tablets, and investigated the relationship between observed amounts of enamel fluoride and incidence of caries. Randomly selected study groups received under supervision either one placebo tablet, one APF tablet containing 1 mg fluoride, or 2 APF tablets (3 hours apart) each school day. An abrasive enamel-type biopsy of a maxillary central incisor was taken 30 months after the start of fluoride tablet treatments at the time of the follow-up examinations. Mean fluoride levels in the biopsied enamel from each of the three groups were similar despite a significant restriction in caries in the group receiving two APF tablets per day. These findings suggest that fluoride can restrict dental caries by some mechanism other than fluoride uptake in the enamel.

Acidulated Phosphate Fluoride↗

Glyburide/metformin tablets: a new therapeutic option for the management of Type 2 diabetes.

Oral antidiabetic combination therapy is a proven means of establishing glycaemic control in the hyperglycaemic, Type 2 diabetic patient, but co-administering two oral antidiabetic agents separately may hinder compliance with therapy. A new single-tablet of glyburide/metformin combination therapy (Glucovance), Bristol-Myers Squibb, Inc.) has recently been developed, which addresses the primary defects of Type 2 diabetes: beta-cell dysfunction and insulin resistance. The glyburide/metformin tablet, taken with meals, is designed to optimise the absorption of glyburide and to address the postprandial glucose rise. Glyburide/metformin tablets are more effective in controlling fasting and postprandial glycaemia than its component monotherapies, at lower doses of metformin and glyburide compared with monotherapy because of the synergy between its glyburide and metformin components. Moreover, a double-blind study showed that glyburide/metformin tablets are more effective than a free combination of glyburide co-administered with metformin in controlling postprandial glucose. Retrospective analyses suggested that glyburide/metformin tablets control glycated haemoglobin (A1C) more effectively than a free combination of glyburide co-administered with metformin, at lower mean doses of glyburide and metformin. The incidence of side effects is lower than separate component therapy for any given A1C. Glyburide/metformin tablets are an effective option for optimising the control of blood glucose in Type 2 diabetic patients and appear to enhance adherence to therapy.

Clinical Trials as Topic↗

Case studies in swelling polymeric gastric retentive tablets.

Swelling tablets administered in the fed state have been shown to provide therapeutic advantages in two marketed products, with the duration of delivery characterised with respect to food and tablet size. Metformin extended-release tablets are a diffusion-based swelling tablet demonstrating once-daily efficacy with good gastrointestinal solubility. Ciprofloxacin extended-release tablets are based on an erosional matrix that delivers the drug to the upper gastrointestinal tract over 6 h to provide once-daily efficacy with reduced incidences of nausea and diarrhoea. Furosemide extended-release tablets are another example of an erosional matrix designed to deliver furosemide to the duodenum and upper jejunum over 6 h to provide a more gradual diuresis and naturesis compared with the immediate-release product.

Administration, Oral↗

Comparative bioavailability study of cefixime administered as tablets or aqueous solution.

The relative bioavailability of cefixime was studied in 24 healthy male volunteers, with each subject receiving a single 400mg dose of cefixime administered as an aqueous solution, a 400mg tablet and two 200mg tablets, in a randomised crossover sequence. Serum and urine samples were analysed using high-performance liquid chromatography. Peak cefixime levels were achieved 3 hours after administration of the solution vs 4 hours for the 2 tablet formulations; however, the extent of absorption was only slightly improved with the solution (by 14 and 7% compared with the 1 x 400 and 2 x 200mg tablets, respectively). The 400mg and 2 x 200mg tablets were found to be bioequivalent. The pharmacokinetic profile of the 400mg cefixime tablet (mean maximum plasma concentrations of 4.4 mg/L at 4 hours, area under the concentration-time curve of 34.4 mg/L.h, and apparent terminal elimination half-life of 3.7 hours) supports the clinical evaluation of a 400mg once-daily dosage regimen for cefixime.

Adult↗

Entacapone/levodopa/carbidopa combination tablet: Stalevo.

Entacapone (Comtess/Comtan) is Orion Pharma's original proprietary catechol-O-methyl transferase (COMT) inhibitor. Entacapone is able to slow down degradation of levodopa and improve the availability and efficacy of each levodopa dose, hence its use as a complement to levodopa/carbidopa in patients with Parkinson's disease. In order to simplify the daily dosing of these medications, Orion has developed an entacapone/levodopa/carbidopa combination tablet. Three tablet strengths are being developed so as to cover the most common clinical dosing needs. In September 2000, Orion signed a marketing and distribution agreement with Novartis for the combination tablet. Under the terms of the agreement, Orion has exclusive marketing rights for the product in Germany, the UK, Ireland, the Nordic and Baltic countries, and several Eastern European countries. Novartis has exclusive rights to the US and territories other than those markets for which Orion holds market exclusivity. Orion also has the option to co-promote the product in France, Spain and several other countries. In June 2003, the US FDA approved the entacapone/levodopa/carbidopa combination tablet (Stalevo) for the treatment of patients with idiopathic Parkinson's disease who experience signs and symptoms of end-of-dose 'wearing off'. Market launch of the product is expected toward the end of 2003 in the US. Also in June 2003, the Committee for Proprietary Medicinal Products of the European Agency for the Evaluation of Medicinal Products adopted a positive opinion of the combination tablet. In September 2002, Orion submitted an application for the approval of the combination product in the European Union. It is expected that the product will be marketed in the European Union in early 2004. Orion estimates that about two of three fluctuating Parkinson's disease patients will be able to be treated effectively with the triple combination tablet.

Administration, Oral↗

Eslicarbazepine acetate (BIA 2-093) : relative bioavailability and bioequivalence of 50 mg/mL oral suspension and 200mg and 800mg tablet formulations.

PURPOSE: To investigate the bioavailability and bioequivalence of three different formulations of eslicarbazepine acetate (BIA 2-093): 50 mg/mL oral suspension (test 1), 200mg tablets (test 2) and 800mg tablets (reference). DESIGN, SUBJECTS AND METHODS: Single-centre, open-label, randomised, three-way crossover study in 18 healthy subjects. The study consisted of three consecutive periods separated by a washout period of 7 days or more. Each subject received a single dose of eslicarbazepine acetate 800mg on three different occasions: 16mL of oral 50 mg/mL suspension, four 200mg tablets or one 800mg tablet. RESULTS: Eslicarbazepine acetate was rapidly and extensively metabolised to BIA 2-005. Maximum BIA 2-005 plasma concentrations (Cmax) and area under the plasma concentration-time curve from time 0 to infinity (AUCinfinity) were, respectively (arithmetic mean +/- SD), 18.0 +/- 4.6 microg/mL and 325.7 +/- 64.9 microg x h/mL for test 1, 16.0 +/- 4.0 microg/mL and 304.2 +/- 66.0 microg x h/mL for test 2, and 17.0 +/- 4.1 microg/mL and 301.1 +/- 60.0 microg x h/mL for the reference formulation. Point estimate (PE) and 90% confidence intervals (CIs) for AUCinfinity test 1/reference geometric mean ratio were 1.09 and 1.01, 1.15; for Cmax ratio, PE and 90% CI were 1.07 and 0.97, 1.15. When test 2 and the reference formulations were compared, the PE and 90% CI were 0.99 and 0.94, 1.07 for the AUCinfinity ratio, and 0.94 and 0.86, 1.02 for the Cmax ratio. Bioequivalence of test versus reference formulations is thus accepted for both AUCinfinity and Cmax because the 90% CIs lie within the acceptance range of 0.80-1.25. CONCLUSION: The pharmacokinetic profiles of eslicarbazepine acetate oral 50 mg/mL suspension, 200mg tablet and 800mg tablet formulations were essentially similar, and the formulations can be considered bioequivalent.

Administration, Oral↗

Oral oxytocics for induction of labor. A randomized study of prostaglandin E2 tablets and demoxytocin resoriblets.

A randomized comparative study of 387 consecutive patients admitted for induction of labor was carried out using two orally administered oxytocics (prostaglandin E2 tablets (Prostin) or Demoxytocin resoriblets for buccal administration (Sandopart)), the results of which are reported here. One-hundred and twenty-three cases were suitable for primary amniotomy; of these 48 were given PGE2 tablets and 75 received demoxytocin resoriblets. In a further 264 cases, primary amniotomy was inadvisable and of these, 133 patients were allotted to the PGE2 treatment group and 131 to treatment with demoxytocin. A significantly higher success rate was observed (p less than 0.05) in the PGE2 group in cases where primary amniotomy had been carried out, as compared with the demoxytocin group. Parturition was successfully induced in 82.0% of the patients given PGE2 tablets, as against only 63.4% of those receiving demoxytocin following 2 days of stimulation without primary amniotomy. This difference is statistically significant at the 0.001 level, and presumably due to the highly significant difference (p less than 0.0001) between patients with a Bishop score of 5 or less, where induction was successful in 75.4% given PGE2 tablets, in contrast to a success rate of only 36.7% in patients receiving demoxytocin resoriblets. No difference was observed in the success rate between the two treatment groups when the Bishop score was 6 or more. No difference was recorded in the incidence of fetal distress, instrumental delivery or low Apgar score between the two treatment groups. However, a higher incidence of vomiting and diarrhea were observed in patients treated with PGE2 tablets (11%) as compared with those receiving demoxytocin (1.5%). There was no difference with regard to the induction-delivery time, nor to the different stages of labor between otherwise comparable treatment groups when the induction was successful. It is concluded in respect of induction of labor using orally administered oxytocics that PGE2 (tablets) are preferable to demoxytocin (resoriblets) as it is the more effective of the two.

Administration, Oral↗

Formulation and release of dihydralazine sulphate from tabletted microcapsules.

One of the principal uses suggested for the microencapsulation of pharmaceuticals has been the preparation of the sustained release dosage form. The finished microcapsules have usually been presented in the form of suspensions or gels, but in order to obtain greater sustained release effect a non-disintegrating tablet would be a better formulation. Dihydralazine sulphate (Nepresol) is a dihydralazine-1,4-phthalazine derivative and used as an antihypertensive drug. This work was planned to prepare sustained action preparations of dihydralazine sulphate by microencapsulation and by tabletted microcapsules. Microcapsules were prepared from the microcapsule fractions using biconvex punches with 0.81 cm diameter fitted into a single punch by hand compressor. Avicel PH 101 and lactose were used as disintegrating materials in tablets having 2 kg hardness. Dissolution from both suspended microcapsules and the tablets was studied using the USP XX basket method. A study of in vitro release for both the free and tabletted microcapsules showed basically the same pattern but the time for the release was extended in the case of the tabletted preparations. Dissolution of dihydralazine sulphate was found to be governed by the core: wall ratio, microcapsule size, and the amount and kind of disintegrating agents. Dissolution kinetics were studied and evaluated.

Capsules↗

Analgesic effect and bioavailability of oral ketogan given as tablets or mixture to patients with chronic pain of malignant origin.

Thirteen cancer patients with moderate to severe chronic pain of malignant origin on treatment with Ketogan tablets were included in an open non-randomized cross-over study comparing the analgesic effect, side effects and serum concentrations of Ketogan tablets and mixture. The patients were six days in hospital and were dosed two days with tablets, two days with mixture and finally another two days with tablets. Recordings of pain and side effects and collection of blood samples prior to dosing and hourly thereafter until remedication were performed on the second day of each dosing period in a morning dose interval. The analgesic effect judged by visual analog score (VAS) and pain intensity differences (PID), the areas under the serum concentration time curves, and the average serum concentrations for the three groups were compared. It was not possible do detect any differences among the three groups concerning the analgesic effect, duration of analgesic effect, the serum concentrations and the side effects. The mean plasma half-life of ketobemidone was 2.74 h +/- 0.90 (SD) and the mean relative bioavailability of the mixture was slightly above 100%. Linear regression analysis revealed a significant correlation between ketobemidone serum concentrations and analgesic effect, VAS, for tablet one and for the mixture but not for tablet two, possibly due to the fixed dosing schedule and to the positive effect of hospitalization on the pain.

Administration, Oral↗

Influence of tablet hardness and hydrophobicity on the adhesive properties of an acrylic resin copolymer.

The adhesive properties--including the force of adhesion, elongation at adhesive failure, the modulus of adhesion, and the adhesive toughness--of an acrylic resin copolymer were determined using the butt adhesion technique. Flat-faced tablets containing up to 30% hydrogenated castor oil were coated with an aqueous dispersion of Eudragit L30D-55. Using data obtained from a Chatillon digital force gauge attached to a motorized test stand, force-deflection profiles, similar to stress-strain curves generated in the tensile testing of free films, were constructed. The surface characteristics of the tablets significantly influenced polymer-substrate interaction. The force of adhesion, the elongation at adhesive failure, and the adhesive toughness decreased as the surface of the tablet became more hydrophobic through the addition of wax to the tablet formulation. Lower adhesive properties were found with increasing tablet hardness, due to a decrease in the effective area of contact between the film coating and the tablet surface. Increased polymer loading resulted in stronger adhesion, indicating a relationship between the mechanical and adhesive properties of the polymer. The present study demonstrated that the area under the force-deflection profile in conjunction with the force of adhesion was more representative of the adhesive properties of the polymer.

Acrylic Resins↗

Controlled-release tablet matrices from carrageenans: compression and dissolution studies.

This study investigates the potential of two commercial carrageenans, Gelcarin GP-379 (iota-carrageenan) and Viscarin GP-209 (lambda-carrageenan) to be used for the preparation of controlled-release tablet matrices. Tablets were compressed on an instrumented Stokes single punch machine and compression characteristics of the carrageenans were analyzed. Heckel plots using out-of-die tablet densities were linear with calculated yield pressures of 81.3 MPa and 105.2 MPa for iota- and lambda-carrageenan, respectively. Drug release from tablet formulations that contained equal amounts of the two carrageenans had near zero-order release profiles. There was little or no effect of tablet compression pressure on the drug release profiles from 70 to 175 MPa. As drug loading was increased from 5 to 20%, the diffusional exponent decreased from 1.056 to 0.678. Thirty percent drug loading resulted in breakup of tablets during dissolution and departure from zero-order release. Multiple regression analysis was used to predict the time for 50% release as a function of the concentration of the two carrageenans and a third filler material, microcrystalline cellulose. Predicted values were in good agreement with observed values and R2 for the final cubic model was 0.9984.

Carrageenan↗

Effect of bicarbonate, phosphate, and saline lavage solutions on the dissolution of ferrous sulfate tablets.

The liberation of iron from ferrous sulfate tablets was studied in vitro to determine the influence of typical lavage solutions used to treat iron poisoning. In separate experiments, one or six tablets were immersed in simulated gastric fluid that contained bicarbonate, phosphate, or normal saline. The amounts of iron liberated from the single tablet studies were not significantly different among the three lavage solutions. In the 6-tablet experiments, the liberation of iron was significantly (p less than 0.05) retarded by bicarbonate and phosphate lavage solutions compared to saline. The clinical significance of these findings is difficult to assess without correlation in vivo. Studies comparing the lavage solutions for iron poisoning should consider the wide intertablet variability in dissolution, the retardation of iron liberation from multiple tablets by bicarbonate and phosphate, and the use of iron tablets instead of iron solutions.

Bicarbonates↗

Comparative bioavailability study of zidovudine administered as two different tablet formulations in healthy adult subjects.

AIM: Zidovudine is a synthetic nucleoside analogue of thymidine with activity against the human immunodeficiency virus type 1 (HIV-1). In patients with HIV infections or the acquired immunodeficiency syndrome (AIDS), zidovudine is a first-line therapy that was shown to reduce morbidity, mortality, and hospitalization. A generic formulation of zidovudine offers the possibility of considerable savings to HIV/AIDS patients in developed and Third World countries. The objective of the current study was to characterize the pharmacokinetic and safety profiles of zidovudine administered as a generic tablet formulation relative to the innovator product. VOLUNTEERS AND METHODS: A total of 68 healthy adult volunteers received a 300 mg oral dose of zidovudine as the generic formulation (AVIRO-Z 300 mg tablet, Ranbaxy Laboratories Limited) and as the innovator product (Retrovir tablet, GlaxoSmithKline) in a randomized, 2-way crossover study. Multiple blood samples were collected over 12 hours and plasma concentrations of zidovudine were assayed using an LC/MS/MS method with an analytical range of 5.00 to 2,000 ng/ml. Pharmacokinetic parameters were calculated using non-compartmental methods. RESULTS: Mean plasma concentrations of zidovudine declined in a mono-exponential manner, with mean concentration values falling below the limit of quantitation 12 hours after administration of both formulations. Mean area under the curve from time 0 to the last measurable concentration (AUC(0-t)), mean area under the curve from time 0 to infinity (AUC(0-infinity)) and peak plasma concentrations (C(max)) of zidovudine for the generic tablet formulation (2,220.6 ng x h/ml, 2,236.0 ng x h/ml and 1,087.9 ng/ml, respectively) were very similar to those observed for the innovator product (2,139.7 ng x h/ml, 2,158.6 ng x h/ml and 1,066.5 ng/ml, respectively). Ratios of least-squares means and 90% confidence intervals of AUC(0-t) AUC(0-infinity) and C(max) between the 2 formulations were within 80-125%, suggesting that the two tablet formulations displayed similar rate and extent of bioavailability. The oral clearance (CL/F) of zidovudine for the generic and innovator formulations were 2.11 1/h/kg and 2.16 1/h/kg, respectively. For the two formulations, adverse events were similar in nature and frequency. CONCLUSION: Since the two formulations displayed similar in vivo delivery rate of zidovudine in the bloodstream, the generic tablet formulation of zidovudine developed by Ranbaxy should be equally effective as the innovator product and is expected to produce considerable cost-savings in AIDS patients worldwide.

Administration, Oral↗

Comparative anti-caries effects of tablet and liquid fluorides in cleft children.

Children with cleft lip and/or palate are at a higher risk for developing caries of the primary incisors compared with non-cleft children. To determine whether fluoride in tablet or liquid form would be more efficacious with children with cleft lip and/or palate, a two-year clinical investigation was conducted to test the anti-caries effects. One-hundred and fifteen cleft children (59 boys and 56 girls) between 22 and 26 months old were randomly selected into control, tablet and liquid fluoride groups. The amount of administered fluoride was 0.25 mg F daily in non-fluoridated Taiwan. Dental examinations were conducted using mirrors and #23 explorers. Caries were assessed using the DMF index in the baseline, first year and second year. The results showed that children in the tablet and liquid groups had a significantly lower DMFT increment than in the control group (p < 0.05). In the DMFS index, children in the liquid group showed a significantly lower caries increment than in the control group (p < 0.01), and children in the tablet group presented a borderline, but non-significant statistical difference when compared with the control group (p = 0.065). No significant statistical difference was found in either DMFT or DMFS between tablet and liquid fluoride administrations (p = 0.521 and p = 0.383, respectively). It is concluded that dietary fluoride supplements in liquid form show efficacy in reducing early childhood caries in the cleft children. Liquid fluoride showed slightly better numerical anti-caries effect than tablet fluoride, which is possibly due to its ease of administration with small children.

Analysis of Variance↗

[Relative bioavailability of effervescent tablet of potassium chloride in healthy volunteers].

AIM: To probe the approach by which the pharmacokinetics and relative bioavailability of endogenous medicinal substances can be studied. METHODS: A randomized three-crossover study was performed in 18 healthy male volunteers. In two of the three study periods, a single 2 g dose of either effervescent tablet or common tablet of potassium chloride was administered; whereas in one of three periods no drug treatment was given to allow the nondrug-related (endogenous) potassium in urine to be determined. In each period the urine samples were collected at the following intervals: 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-24, 24-48 h after dose. Urine potassium was determined and the cumulative urine potassium-time data were fitted to a one-compartment model with first-order absorption. Bioavailability was represented by cumulative amount of potassium excreted in urine during 48 hours after drug administration and the bioequivalence of the two formulations was evaluated by analysis of variance and two one-sided t-test. RESULTS: The pharmacokinetic parameters were as follows: effervescent tablet T1/2 ke = (6 +/- 5) h, T1/2 ka = (0.08 +/- 0.08) h, ku = (0.09 +/- 0.04) h-1, Xmax/f = (18 +/- 8) mmol; common tablet T1/2 ke = (8 +/- 5) h, T1/2 ka = (0.11 +/- 0.11) h, ku = (0.07 +/- 0.04) h-1, Xmax/f = (18 +/- 8) mmol. Relative bioavailability of effervescent tablet was 97.5% +/- 15.2% compared with common tablet. CONCLUSION: The two formulations were of bioequivalence. The methods used in this study might be applicable to other similar studies involving endogenous medicinal substances.

Adult↗

Bioavailability and stability of erythromycin delayed release tablets.

BACKGROUND: Erythromycin is available as the free base, ethylsuccinate, estolate, stearate, gluceptate, and lactobionate derivatives. When given orally erythromycin and its derivatives except the estolate are inactivated to some extent by the gastric acid and poor absorption may result. OBJECTIVES: To establish whether delayed release erythromycin tablets meet the bioequivalent requirement for the market. METHODS: Sectrophotometric analysis was used to determine the dissolution percentage of the tablets in vitro. High performance liquid chromatography and IBM/XT microcomputer was used to determine the bioavailability and pharmacokinetic parameters in vivo. RESULTS: Dissolution percentage in thirty minutes reached 28.9% and in sixty minutes erythromycin was completely released. The parameters of the delayed release tablets were Tlag 2.3 hr, Tmax.4.5 hr, and Cmax 2.123 g/ml Ka 0.38048 hr(-1) T (1/2) 1.8 hr, V*C/F 49.721 AUC 12.9155. The relative bioavailability of erythromycin delayed release tablet to erythromycin capsules was 105.31% CONCLUSION: The content, appearance, and dissolution bioavailability of delayed release erythromycin tablets conforms to the United States pharmacopoeia standards. The tablets should be stored in a cool and dry place in airtight containers and the shelf life is temporarily assigned two years.

Administration, Oral↗

[Bioequivalence and bioavailability after single administration of effervescent ranitidine tablets].

An open two-way cross-over study in 12 healthy male volunteers was performed in order to determine the relative bioavailability of a 150 mg ranitidine (Zantic, CAS 66357-35-5) effervescent tablet sweetened with saccharine in comparison to the 150 mg standard ranitidine dispersible tablet (Trinkette). On two occasions separated by a wash-out period of 1 week volunteers received a single oral dose of both formulations. On each administration day blood samples were collected at predetermined time points in order to investigate the pharmacokinetic parameters. Single oral doses of ranitidine were very well tolerated by healthy male volunteers. The non-parametric 95% confidence intervals for AUC and Cmax were 87 to 116% and 84 to 107%, respectively. The relative bioavailability of the ranitidine effervescent tablet was 99% compared to the dispersible tablet. The mean of the Cmax ratio was 95%. The ranitidine effervescent tablet could thus be claimed to be bioequivalent to the dispersible tablet.

Adult↗

[Effects of Huobahuagen tablet on the expression of interleukin-3 receptor mRNA in asthmatic guinea pig bronchoalveolar lavage fluid and eosinophil infiltration].

OBJECTIVE: To investigate the effects of Huobahuagen tablet on the expression of interleukin-3 (IL-3) receptor mRNA in bronchoalveolar lavage fluid (BALF) and infiltration of eosinophil (Eos) in the airway of asthmatic guinea pigs. METHODS: Thirty-two healthy guinea pigs were randomized into 4 equal groups, the control group, asthmatic group, dexamethasone therapy group and Huobahuagen tablet therapy group. Asthma was induced in the latter 3 groups which were challenged with the asthma-inducing agents and at the same time received treatments as indicated. BALF were collected subsequently from the guinea pigs for examining the total cell number and cell classification, and histopathologic examination of the lung tissue was performed. Semi-quantitative analysis with reverse transcriptional-polymerase chain reaction (RT-PCR) of IL-3 receptor mRNA in the BALF was performed. RESULTS: Compared with the control and the asthmatic group, the number of Eos in the BALF of Huobahuagen tablet therapy group was significantly lower (P<0.05 and P<0.01, respectively). In spite of the presence of hyperemia and edema in the lung tissues of the Huobahuagen tablet therapy group, Eos infiltration was less severe than that in the asthmatic group. As found by RT-PCR, the quantity of IL-3 receptor mRNA in the BALF of the Huobahuagen tablet therapy group did not significantly differ from that in the dexamethasone therapy group, but was significantly higher than that in both the control and asthmatic group (P<0.01). CONCLUSION: Huobahuagen tablet can significantly lower the number of Eos in the airway of asthmatic guinea pigs, a finding that may potentially serve as the elementary theoretical basis for clinical therapy of asthma.

Animals↗