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At least 253 records · Page 14Linked to original sources

PubMed2004

A dynamic artificial gastrointestinal system for studying the behavior of orally administered drug dosage forms under various physiological conditions.

PURPOSE: The purpose of this study was to demonstrate the potential of a dynamic, multicompartmental in vitro system simulating the human stomach and small intestine (TIM-1) for studying the behavior of oral drug dosage forms under various physiological gastrointestinal conditions. METHODS: Two model drug compounds were studied in TIM-1: a lyophilized Lactobacillus strain and paracetamol (acetaminophen). The Lactobacillus survival rate was determined by bacterial counting in the gastric and ileal effluents while simulating the conditions of the gastrointestinal tract of infants or adults. The availability for absorption of paracetamol from two oral dosage forms was investigated by measuring the drug concentration in jejunal dialysis fluid. The effect of gastrointestinal passage time and food intake on paracetamol absorption was also studied. RESULTS: The Lactobacillus survival rate in both gastric and ileal effluents was higher during simulation of the infant compared to adult conditions. We also showed that (i) paracetamol absorption was faster when it was administered as a free powder than in sustained-release tablet form, (ii) a slow passage time resulted in a delay in the absorption of paracetamol, and (iii) there was a lower rate of absorption when paracetamol was ingested with a standard breakfast as opposed to water. The in vitro results were consistent with in vivo data, showing the predictive value of TIM-1. CONCLUSIONS: TIM-1 is a powerful tool for supplying valuable information about the effects of various gastrointestinal conditions on biopharmaceutical behavior and efficacy of drug delivery systems in the development of oral formulations.

Acetaminophen↗

PubMed2001

A new 5-aminosalicylic acid multi-unit dosage form for the therapy of ulcerative colitis.

The aim of the present study was to develop a multi-unit dosage form containing 5-aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis (UC), optimised on the basis of recent studies indicating that UC patients have higher intestinal pH than was previously thought to be the case. Pellets with a drug content of 77.4% were prepared by a granulation and spheronization process and then coated with a new pH sensitive poly(meth)acrylate copolymer (Eudragit((R)) FS 30D) to achieve site specific drug release close to the ileocecal valve. Dissolution tests were carried out in a paddle dissolution apparatus in media simulating pH conditions at various locations in the gastrointestinal tract. The pellets released rapidly at pH values above 7.5. Between 6.8 and 7.2 drug release was found to be zero order, while at pH 6.5 and below no release occurred. In a biorelevant medium which simulates the fasting proximal small intestine fluid it was shown that neither surfactants (sodium taurocholate and lecithin) nor changes in ionic strength trigger drug release. Compared to 5-ASA pellets coated with the well established Eudragit((R)) S, and to currently marketed products licensed for the treatment of UC, the multi-unit dosage form coated with the new polymer exhibited an in vitro dissolution profile more appropriate to the pH profile of the ileum and the colon observed in UC patients.

Acrylates↗

PubMed1994

Treatment of hypertensive emergency. Comparison of a new dosage form of the calcium antagonist nitrendipine with nifedipine capsules.

OBJECTIVE: To present the efficacy and tolerability of a new oral dosage form of the calcium antagonist nitrendipine compared to nifedipine capsules in patients with hypertensive emergency. DESIGN: Multicenter randomized double blind clinical study. SETTING: 23 study centres (hospitals) in Germany. PATIENTS: 161 patients between 20 and 70 years with acutely elevated blood pressure (systolic 200-250 mmHg, diastolic between 110-140 mmHg) with and without concomitant clinical symptoms. INTERVENTIONS: Double blind treatment with 10 mg nifedipine or 5 mg nitrendipine. Nifedipine was administered as capsules, nitrendipine was given from a small plastic tube (vial), containing 1 ml alcoholic solution. Every patient received in addition to the test medication a placebo corresponding to the other product. Patients with insufficient treatment after 45 min were given either an additional capsule of 10 mg nifedipine or a further vial containing 5 mg nitrendipine according to their group and maintaining the double dummy procedure. MEASUREMENTS AND RESULTS: Blood pressure and heart rate were measured repeatedly during 4 h, before and 90 min after beginning of the treatment a 12 channel resting ECG was recorded. At 45 min after administration the blood pressure had fallen significantly from 216.0/117.4 mmHg to 170.0/93.3 mmHg under nifedipine and from 216.9/117.3 mmHg to 177.4/94.4 mmHg under nitrendipine. 61.6% of the nifedipine patients and 58.8% of the nitrendipine patients had already reached blood pressure values < 180/100 mmHg after 45 min and in both groups 83% of these patients were still in this limit at the end of the observation period after 4 h. Tolerability was very good in both groups. CONCLUSION: The new dosage form of nitrendipine (vial with 1 ml of alcoholic solution) represents an alternative in the treatment of hypertensive emergency.

Administration, Oral↗

PubMed2001

Pyrocatechol violet in pharmaceutical analysis. Part I. A spectrophotometric method for the determination of some beta-lactam antibiotics in pure and in pharmaceutical dosage forms.

A fairly sensitive, simple and rapid spectrophotometric method for the determination of some beta-lactam antibiotics, namely ampicillin (Amp), amoxycillin (Amox), 6-aminopenicillanic acid (6APA), cloxacillin (Clox), dicloxacillin (Diclox) and flucloxacillin sodium (Fluclox) in bulk samples and in pharmaceutical dosage forms is described. The proposed method involves the use of pyrocatechol violet as a chromogenic reagent. These drugs produce a reddish brown coloured ion pair with absorption maximum at 604, 641, 645, 604, 649 and 641 nm for Amp, Amox, 6APA, Clox, Diclox and Flucolx, respectively. The colours produced obey Beer's law and are suitable for the quantitative determination of the named compounds. The optimization of different experimental conditions is described. The molar ratio of the ion pairs was established and a proposal for the reaction pathway is given. The procedure described was applied successfully to determine the examined drugs in dosage forms and the results obtained were comparable to those obtained with the official methods.

Anti-Bacterial Agents↗

PubMed2001

Modification of crystal habit and its role in dosage form performance.

Crystallization is often employed for purifying a drug substance. Use of different solvents and processing conditions may change the crystal habit, besides altering the polymorphic state. Furthermore, altered habit may result from crystal growth during storage. Hence, there is a need to understand the factors influencing crystal habit and to evaluate critically, its role in the performance of dosage forms. Establishing the physicotechnical properties of different habits of a drug will help to recognize lot-to-lot variations in raw materials and to ensure reproducibility of dosage form performance.

Algorithms↗

PubMedDate not supplied

Nuclear magnetic resonance spectroscopic determination of dicyclomine hydrochloride in tablet, capsule, and injection dosage forms.

A rapid and specific nuclear magnetic resonance (NMR) spectroscopic method was developed for determining dicyclomine hydrochloride in tablet, capsule, and injection dosage forms. The method consists of an extraction step with chloroform, evaporation of the solvent, addition of maleic acid as an internal standard, dissolution of the mixture in deuterated chloroform-deuterated acetone (40 + 60), NMR spectral determination, and integration of the peaks of interest. The concentration of dicyclomine hydrochloride in the dosage form was calculated from the integral values for the peaks of the test compound and the internal standard. The average recovery value +/- the standard deviation (n = 5) of dicyclomine hydrochloride added to synthetic samples was 99.7 +/- 0.9% (coefficient of variation 0.9%). The assay values for various commercial tablets, capsules, and injectables analyzed by using the proposed method differed in all cases by less than 1% from those obtained by using the USP XX titrimetric method. There was no interference from stearate, an excipient found in tablets and capsules, or from chloral hydrate, a preservative found in injectables .

Capsules↗

PubMed2003

A statistical support for using spectroscopic methods to validate the content uniformity of solid dosage forms.

The advent of PAT, Process Analytical Technologies, offers the possibility of large scale monitoring of tablets as they come off the press. The most rapid techniques allowing the largest sample sizes are based on reflectance spectroscopy. As these techniques sample only a portion of the tablet, it is critical to prove that sampling a portion has a larger (and, therefore, more conservative) statistical variance than sampling the entire. Once demonstrated, a partial sampling technique, for example, a Near Infrared (NIR) sensor, should be able to provide a safe bracket for content uniformity evaluation. It is the purpose of this report to support the claim that the coefficient of variance (CV) from sampling a part of a dosage form cannot be smaller than the CV from sampling the whole dosage form. This hypothesis will be supported in this study by both a statistical proof and experimental data acquired from a model tablet system.

Chromatography, High Pressure Liquid↗

PubMed2003

Lyophilization of unit dose pharmaceutical dosage forms.

A lyophilization process for a pharmaceutical unit dosage form was developed which comprised a container closed with an impermeable membrane pierced with one or more holes through which the material in the container can be lyophilized. The hole or holes in the membrane have to be sufficiently large to allow water vapor to escape but small to ensure that the material is kept within the container. Lyophilization from sealed, perforated, unit-dose package has shown to be feasible. The technique offers a novel convenient means of lyophilizing nonsterile products in their primary pack and increases the potential for the development of lyophilized formulations for nonparenteral applications.

Drug Contamination↗

PubMed1988

Gastric emptying of large single unit dosage forms.

The gastrointestinal transit of two single unit dosage forms has been followed in healthy subjects under different feeding conditions. Transit was affected by the size of the meal administered. When two tablets were given concurrently they often emptied from the stomach at or about the same time, but in a number of cases the two units were seen to empty at widely different times.

Adolescent↗

PubMed1990

Determination of flubendazole in pharmaceutical dosage forms by differential pulse polarography and UV spectroscopy.

A precise and accurate differential pulse polarographic method was developed for the determination of flubendazole in dosage forms without any prior extraction procedure of interference from the other stated ingredients. A UV spectroscopic procedure was also described and used as reference method. Analyses were generally performed at the 4 micrograms ml-1 flubendazole level. Flubendazole or its dosage forms were dissolved in 70% perchloric acid and diluted with a pH 2.6 sodium phosphate-citric acid buffer as polarographic supporting electrolyte or spectrophotometric solvent. The peak potential occurred at about -0.9 V (vs. Ag/AgCl reference electrode), depending on the pH of the assayed solution. The irreversible electrochemical reduction involved the transfer of two electrons. The UV absorption spectrum showed a sharp maximum at 237 nm with a specific extinction coefficient of 886. No advantage was found in the use of first and second-order derivative spectrophotometry.

Indicators and Reagents↗

PubMedDate not supplied

Piroxicam fast-dissolving dosage form in the treatment of patients with acute low back pain.

An open-label, noncomparative study of the efficacy and tolerability of a once-daily piroxicam fast-dissolving dosage form (FDDF) comprised 157 patients aged 15 to 76 years (56.7% men) with acute low back pain of not more than 48 hours' duration. Patients received 40-mg piroxicam FDDF once daily for the first 2 days and 20 mg once daily for up to a total of 14 days of treatment. Fifteen investigators in three countries examined patients at baseline and at follow-up visits on days 4, 8, and 15. All efficacy assessments-including general low back pain; pain on sitting, standing, and walking; overall severity of night pain; duration of morning stiffness; lumbosacral tenderness on moderate pressure; modified Schober test of ability to bend forward; restriction of passive motion; length of time to resumption of an activity impaired by back pain; and overall restriction of back motion-demonstrated statistically significant improvements from baseline at each follow-up visit. Relief of pain, noted 30 minutes after the first dose, was maintained for the 24-hour dosing interval during the first 3 days. At visit 4, after piroxicam FDDF treatment had been completed, the number of patients being assessed had declined by half, principally because the resolution of symptoms had prompted discontinuation of the study drug. At the end of the treatment, 82.9% of patients evaluated the efficacy of piroxicam FDDF as good or excellent and investigators rated efficacy as good or excellent in 85.6% of patients. Tolerability was also rated highly, with 91% of patients characterizing piroxicam FDDF treatment as good or excellent, and investigators rating the treatment as good or excellent in 92% of patients. In all, 12.7% of the patients experienced drug-related adverse events, most frequently involving the gastrointestinal system. Drug-related adverse experiences prompted discontinuation of the study medication in five (3.2%) patients. These results suggest that the newly developed dosage form, piroxicam FDDF, administered in a dosage of 40 mg/d for the first 2 days and 20 mg/d thereafter (for up to 14 days), is effective and well tolerated in the treatment of patients with acute low back pain.

Adolescent↗

PubMed2004

Thermal analysis study of the interactions between acetaminophen and excipients in solid dosage forms and in some binary mixtures.

Thermogravimetry (TG) and differential scanning calorimetry (DSC) were used to assess the compatibility between acetaminophen (Ac) and some excipients (polyvinylpyrrolidone (P), magnesium stearate (M), citric acid (C), aspartame (As), mannitol (Mn), cellulose (Cll) and starch (S)) in several of the more commercially available pharmaceutical formulations and in solid binary mixtures. The present study compared thermodynamic data on acetaminophen melting and vaporization processes of pure acetaminophen with those found for several solid mixtures and in some commercially available acetaminophen-based dosage forms. Appreciable modifications occur only for solid mixtures with high content of excipient. Acetaminophen-based dosage forms and its solid binary mixtures usually show "additivity" of calorimetric peaks number of pure components in their calorimetric curve profiles, thus revealing a good thermoanalytical compatibility between acetaminophen and the excipients examined, except for samples containing appreciable content of mannitol.

Acetaminophen↗

PubMed1997

Pharmacokinetic-pharmacodynamic modelling as a tool to evaluate the clinical relevance of a drug-food interaction for a nisoldipine controlled-release dosage form.

OBJECTIVE: Nisoldipine, a calcium antagonist of the dihydropyridine class, has been used in the treatment of hypertension and angina pectoris. A new controlled-release dosage form (nisoldipine coat-core, NCC) has been developed to allow once daily dosing. In addition to a formal food interaction study as requested by regulatory authorities for controlled-release dosage forms, a subsequent study was conducted to determine the clinical relevance of the changes in nisoldipine plasma concentration vs time profiles seen in the food effect study. METHODS: After a placebo run-in phase of 6 days, 12 hypertensive patients started treatment with 20 mg NCC once daily (days 0-3, 5-6, 8-9). On days 4, 7 and 10 the NCC was substituted for 5, 10 and 20 mg nisoldipine solution, respectively, in order to obtain nisoldipine plasma concentration vs time profiles comparable to the ones resulting from the concomitant intake of food and NCC. Simultaneous measurements of blood pressure (BP) and nisoldipine concentration were performed on days 3, 4, 7 and 10. RESULTS: The relationship between nisoldipine plasma concentrations and percentage reduction in BP [diastolic (DBP) and systolic (SBP), supine and standing] could be described by an Emax model. The mean maximum reduction (Emax) relative to baseline was about 36.4% and 37.7% (DBP, supine and standing) and 27.9% and 29.2% (SBP, supine and standing), respectively. The interindividual variability (% CV) in Emax was low, ranging from 17.6% to 28.8%. The mean nisoldipine plasma concentration corresponding to 50% of the maximum effect (EC50) ranged between 0.99 and 2.62 micrograms.l-1 with a pronounced interindividual variability (% CV) of 89.5-108.8%. Mean Cmax values after administration of the 30 and 40 mg NCC together with food were 4.5 and 7.5 micrograms.l-1, respectively. Based on the concentration-effect relationship established in the present study, the effect achieved with a concentration of 7.5 micrograms.l-1 will be about 77% of Emax for DBP and about 88% of Emax for SBP, respectively. CONCLUSION: At the time of maximum plasma concentration the additional decrease in BP relative to baseline due to the food effect will be about 7-15% for DBP and 3-9% for SBP. After administration of the 10 mg solution with a mean Cmax of 8.7 micrograms.l-1, only headache and flush with mild severity have been reported as adverse events. These maximum concentrations are comparable to Cmax values seen after intake of 40 mg NCC with food. With regard to heart rate (HR) there were distinct differences between the two formulations: Following administration of 5, 10 and 20 mg nisoldipine solution, there were dose-dependent increases in HR by a maximum of 4, 12 and 16 beats.min-1, respectively, whereas the HR profile for the NCC was similar to that seen under placebo treatment.

Adult↗

PubMed2001

Spectrofluorimetric determination of streptomycin in dosage forms and in spiked plasma using 9,10-phenanthraquinone.

A simple and highly sensitive method is proposed for the fluorimetric determination of streptomycin in dosage forms and in biological fluids. The method involves the reaction of streptomycin with 9,10-phenanthraquinone in alkaline medium to give a highly fluorescent derivative. The experimental parameters were carefully studied and incorporated into the procedures. The results obtained compared favourably with those obtained by the official methods. The concentration-fluorescence plots were rectilinear over the range 0.025-0.4 microg/ml, with minimum detectability (S/N=2) 0.006 microg/ml (4.19x10(-9) M). The proposed method was applied for the determination of streptomycin in dosage forms. The results obtained were in good agreement with those obtained by the official method. The proposed method was further applied to the determination of streptomycin in human plasma. The percentage recovery was 101.82. A proposal of the reaction pathway was presented.

Indicators and Reagents↗

PubMed2001

[Application of pH-responsive polymers to oral dosage forms for insulin].

The potential of graft copolymer networks with poly(methacrylic acid-g-ethylene glycol; P(MAA-g-EG)) for oral dosage forms to enhance insulin absorption is reviewed. The polymer exhibited unique pH-responsive characteristics in which interpolymer complexes were formed and dissociated, respectively, in acidic and neutral/basic environments. Correspondingly, the polymer was capable of highly incorporating and rapidly releasing insulin in vitro. This insulin loaded polymer successfully enhanced oral insulin absorption in rats with significant hypoglycemic effects. The polymer was also shown to possess mucoadhesive properties. Furthermore, the polymer demonstrated high calcium binding which may affect the proteolytic activity of calcium-dependent enzymes and/or reduce transepithelial resistances. Thus, the polymer has the potential to be used as a carrier for oral dosage forms of insulin to enhance its mucosal absorption.

Administration, Oral↗

PubMed1992

Influence of formulation, receptor fluid, and occlusion, on in vitro drug release from topical dosage forms, using an automated flow-through diffusion cell.

An automated flow-through diffusion cell apparatus was used for comparing the release rates of a naphthoic acid derivative, CD 271, from different topical formulations. The influence of the following parameters on CD 271 release from the formulations was investigated: receptor fluid composition, occlusion, weight of tested formulation, and dosage form type. The amount of tested formulation was shown to have no significant effect on the apparent release constant and lag time for an anionic oil-in-water emulsion and an aqueous gel. Occlusion affected drug release from the different dosage forms. Thus, occlusion increased CD 271 pharmaceutical availability for a lotion and a hydroalcoholic gel containing 0.1% of solubilized drug. The release profile of CD 271 from the formulations was highly dependent on the receptor fluid composition. Drug release was dramatically enhanced with n-octanol as compared to an aqueous solution of surfactant. Using occlusive or nonocclusive procedures, CD 271 apparent release constant and lag time were found to be highly dependent on the type of tested formulation. The flow-through diffusion cell proposed in the present study allows an accurate comparison of drug release characteristics from prototype topical formulations and therefore represents a valuable tool for formulation research or quality control process.

Adapalene↗

PubMed1999

Determination of ephedrine, theophylline and phenobarbital in a tablet dosage form by capillary electrophoresis.

A capillary electrophoresis method was developed to separate and quantitate ephedrine (ED), theophylline (TP) and phenobarbital (PB) in a tablet dosage form. Tablets were ground and extracted with methanol using ultrasonication. Aliquots of standard stock solution were hydrodynamically injected for 5 s at the anodic end. Separation was performed on a fused silica capillary (72 cm x 50 microm i.d.; 50 cm to detector) at an applied voltage of 20 kV with a phosphate run buffer (pH 8.0, 50 mM). Analysis was performed at ambient temperature (23+/-1 degrees C) and the total run time was 9 min with detection at 220 nm. Calibration curves were prepared for ED, TP and PB with methyl p-hydroxy benzoate as internal standard. For each analyte, the correlation coefficients were >0.999 (n = 4). The RSD% of ten replicate injections for each analyte were <1%. The method was applied to the quantitation of ED, TP and PB in a commercial tablet dosage form.

Calibration↗

PubMed1993

Controlled-release isosorbide dinitrate pellets. Part I: Design and evaluation of controlled-release capsule dosage form.

Design and evaluation of 8-h controlled-release isosorbide dinitrate capsules representing 20.0 and 40.0 mg of the drug are described. The formulation conforms to the total drug incorporated in the dosage form. In vitro dissolution studies indicate that the formulations behave as controlled-release dosage forms. Studies of storage at 30 +/- 2 and 40 +/- 2 degrees C at relative humidities of 72.0 and 90.0%, respectively, indicate that both temperature and humidity accelerate the degradation of the formulation. These results indicate the need of controlled packaging conditions during manufacture of these capsules.

Body Fluid Compartments↗