Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DOSAGE FORMS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,675 records · Page 93Linked to original sources
PubMed1990

Effects of various granulating systems on the bioavailability of naproxen sodium from polymeric matrix tablets.

Naproxen sodium and a cellulose ether derivative were granulated with either water or a poly(meth)acrylic acid ester copolymer aqueous dispersion to make three controlled-release matrix dosage forms. The different polymeric matrix systems contained hydroxypropyl methylcellulose (formulation A), hydroxypropyl cellulose:poly(meth)acrylic acid ester copolymer (formulation B), and hydroxypropyl methylcellulose:poly(meth)acrylic acid ester copolymer (formulation C). All three hydrophilic matrix tablets demonstrated identical in vitro dissolution rates. The three controlled-release formulations were compared with a marketed immediate-release naproxen sodium dosage form (formulation D) in a single-dose crossover study in six healthy volunteers. The AUC values for controlled-release dosage forms A and C were larger than those for formulations B and D. However, the reasons why the AUC for formulations A and C is larger than that for formulations B versus D can be explained differently. Formulations A and C more effectively maintain naproxen plasma levels than formulation D by reducing the amount of naproxen unbound to plasma proteins, therefore reducing naproxen available for urinary excretion. Naproxen sodium delivered from formulations A and C is also probably much better absorbed than from that from formulation B, possibly due to less drug entrapment. More importantly, although all three CR formulations had identical in vitro dissolution profiles, naproxen sodium plasma levels were better maintained (based on AUC) in subjects taking formulations A and C, which contained a lower polymer content and did not use hydroxypropyl cellulose. The tmax values were larger for the three controlled-release dosage forms. Also, the Cmax value for the conventional dosage form was nearly twofold higher than that observed for the controlled-release dosage forms.

Adult↗
PubMed1980

Bioavailability of microsize and ultramicrosize griseofulvin products in man.

The relative bioavailability of ten marketed dosage forms of griseofulvin was evaluated in two separate crossover studies. Each study utilized 12 healthy subjects, with eight of the subjects being common to both studies. Plasma griseofulvin concentrations were determined 1, 2, 3, 4, 6, 8, 10, 25, 34, 49, and 73 hr after dosing, using a high-pressure liquid chromatographic method. The "high-dose" study compared four microsize dosage forms administered as 500-mg doses and two ultramicrosize formulations given as 250-mg doses. The "low-dose" study employed four 250-mg microsize products and two 125-mg ultramicrosize products. The individual plasma level-time profiles for the majority of doses suggested prolonged absorption of microsize griseofulvin. The ultramicrosize dosage forms exhibited peak concentrations which were not significantly different (p > 0.05) from those of the microsize products administered as twice the dose. In the high-dose study, the two 250-mg ultramicrosize dosage forms exhibited areas under the plasma level-time curve (AUC) which were significantly (p < 0.05) less than the AUCs for all but one of the 500-mg microsize products. In the low-dose study the AUCs for the ultramicrosize products were significantly lower than the AUCs for all of the microsize dosage forms. Significant differences were also noted among the AUCs for the microsize products, although the maximum difference was less than 20% in both studies. A comparison of the AUCs observed in the high- and low-dosage studies revealed that the AUCs for two of the 500-mg microsize dosage forms were only approximately 75% the AUC predicted from the 250-mg dose for the eight subjects common to both studies. All other formulations exhibited a dose proportionality for AUC.

Adult↗
PubMed1995

Multiple-dose pharmacokinetics and bioequivalence of L-carnitine 330-mg tablet versus 1-g chewable tablet versus enteral solution in healthy adult male volunteers.

The bioavailability and bioequivalence of three oral dosage forms of L-carnitine were studied in 15 healthy volunteers. Recently, an intravenous (iv) dosage form of L-carnitine has been approved to be marketed in the United States. The purpose of this study was to determine after multiple dose administration of the three oral dosage forms (marketed solution, chewable tablet, and marketed tablet) the pharmacokinetics and absolute bioavailability of each of the dosage forms at steady state and compare them with those following administration of a single iv dose. The relative bioavailability and bioequivalence of the chewable and marketed tablet relative to the marketed solution at steady-state replicate design conditions were also studied. Bioavailability based on data that was not corrected for the baseline (uncorrected data) was compared with bioavailability determined from data corrected for baseline. Steady-state conditions, based on free or total L-carnitine plasma concentrations, were achieved by Day 3, and products were bioequivalent based on the analysis of variance and comparisons by the two one-sided t test. Pharmacokinetic evaluations were found to be powerful tools for bioequivalence determinations; the power to detect 20% differences in AUC, Cmax tmax, and Cmin0 was > 80%. Mean absolute bioavailabilities (based on free or total L-carnitine plasma concentrations) on Day 4 (fraction of the dose absorbed) of Carnitor (levocarnitine) tablet, Carnitor (levocarnitine) oral solution, and levocarnitine chewable tablet relative to the first iv dose were approximately 18%. Similarly, absolute bioavailability compared with the last iv dose was approximately 18% for all three oral formulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2003

Stability of sotalol in two liquid formulations at two temperatures.

BACKGROUND: Sotalol is used in certain pediatric patients to treat, suppress, or prevent the recurrence of life-threatening ventricular arrhythmias. However, it is commercially unavailable in a liquid dosage form. The use of an extemporaneously prepared liquid dosage form must be supported by the documentation of the chemical and physical stability of sotalol. OBJECTIVE: To determine the stability of sotalol hydrochloride extemporaneously prepared from tablets in 2 oral suspensions stored at 2 temperatures. METHODS: Five bottles contained Ora Plus:Ora Sweet (1:1) and the other 5 bottles had 1% methylcellulose:simple syrup NF (1:9), with a sotalol concentration of 5 mg/mL. Three samples were collected from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days and analyzed by a stability-indicating HPLC analytical method (n = 15). RESULTS: At 4 degrees C, the mean concentration of sotalol was at least 98.9% of the original concentration in Ora Plus:Ora Sweet suspension and 95.5% of the initial concentration in 1% methylcellulose:simple syrup during storage for 3 months. At 25 degrees C, the mean concentration of sotalol was >/=95.5% of the original concentration in Ora Plus:Ora Sweet suspension and 94.4% of the initial concentration in 1% methylcellulose:simple syrup during storage for 3 months. The pH did not change substantially during the study period. Further, no changes in physical appearance were seen during the study. CONCLUSIONS: Sotalol hydrochloride can be prepared in either of 2 liquid dosage forms and stored in plastic bottles for 13 weeks at 4 or 25 degrees C without substantial loss of potency.

Administration, Oral↗
PubMed2006

Comparative drug release measurements in limited amounts of liquid: a suppository formulation study.

A novel method for the investigation of drug formulations in limited liquid volumes is presented. The experimental setup consists of a measurement cell containing an absorbent sponge cloth placed between two parallel electrodes. Conductivity measurements are used to monitor the drug release from the dosage form. By varying the amount of water contained in the absorbent cloth surrounding the dosage form, it is possible to measure the drug release performance of the dosage form in very limited amounts of water. The method was employed to test four different tablet formulations consisting of the model drug NaCl incorporated in excipient matrices of hard fat, polyethylene glycol, microcrystalline cellulose and a mixture of microcrystalline cellulose and croscarmellose sodium (Ac-Di-Sol). The drug release rates of the different formulations in limited water volumes differed markedly from the release rates in an excess of water. Whereas the release rates from all tablet types in an excess of water showed only minor differences among the tablet types, the release rates from the tablets formulated with disintegrating excipients were clearly superior in limited water volumes. The developed method for drug release in limited volumes of liquid should be suitable for evaluation of rectal dosage forms.

Biological Availability↗
PubMed1984

High-performance liquid chromatographic determination of acid-catalyzed degradation products of methyl carboprost in a polymeric controlled-release device.

A normal-phase high-performance liquid chromatographic method was used for the determination of methyl carboprost and acid-catalyzed degradation products in a polymer-based, controlled release dosage form. A reversed-phase method was used to isolate sufficient quantities of the degradation products to determine their identity. Degradation of methyl carboprost under acidic conditions results in epimerization and dehydration, to several isomers, at the tertiary allylic hydroxyl group. Mass balance was 94% for a sample allowed to degrade 50%. These compounds were observed to form in the polymer-based, controlled release dosage form. For the determination of methyl carboprost in the dosage form, the method was found to be linear, precise with a relative standard deviation of 2% and to have an average recovery of 99.2%.

Carboprost↗
PubMed1990

The development of USP dissolution and drug release standards.

Dissolution tests have been in use in the pharmaceutical industry for over 20 years, and they are official in The United States Pharmacopeia since the early 1960s. The dissolution test, reviewed primarily as a quality control tool, replaced the use of disintegration tests which had been official in The United States Pharmacopeia since 1950. Refinements in the dissolution test equipment and methodology have occurred over the years in order to enhance its relevance. The Subcommittees of the USP Committee of Revision dealing with these issues have developed and refined compendial dissolution standards and policies for conventional solid-oral dosage forms and modified-release dosage forms.

Delayed-Action Preparations↗
PubMed1998

[Manufacture and in vitro characterization of a new fluid theophylline sustained-release form. Sachets with microcapsules for administration in a drinkable sustained-release suspension].

The administration of currently available theophylline (CAS 58-55-9) sustained release preparations with high drug doses (hard capsules, tablets) presents difficulties for certain patient groups as children and elderly, due to the large geometry of these dosage forms. Therefore, a suspension for easy administration based on the novel Liquitard technology was developed using theophylline microcapsules. This paper describes the manufacturing procedure of the new dosage form and its in vitro release characteristics as a function of various parameters. During manufacturing, the suspension-forming excipients are first granulated and then filled into sachets together with the microcapsules. The sustained release suspension is prepared by the patient himself immediately before administration. The in vitro release of theophylline from the dosage form is neither affected by the suspension-forming excipients nor by the drug amount. This allows for the manufacture of sachets with different drug strength maintaining the same qualitative composition. Furthermore, the in vitro release is independent of pH, osmolality, agitation and of the addition of surfactants and native bile to the dissolution medium. The new dosage form thus meets the current EC-guidelines for oral sustained release dosage forms. The in vitro limits of the dissolution testing were verified on the basis of the bioequivalence of the batches at the upper and lower specification limits.

Anti-Asthmatic Agents↗
PubMed2006

Buccal bioadhesive drug delivery--a promising option for orally less efficient drugs.

Rapid developments in the field of molecular biology and gene technology resulted in generation of many macromolecular drugs including peptides, proteins, polysaccharides and nucleic acids in great number possessing superior pharmacological efficacy with site specificity and devoid of untoward and toxic effects. However, the main impediment for the oral delivery of these drugs as potential therapeutic agents is their extensive presystemic metabolism, instability in acidic environment resulting into inadequate and erratic oral absorption. Parenteral route of administration is the only established route that overcomes all these drawbacks associated with these orally less/inefficient drugs. But, these formulations are costly, have least patient compliance, require repeated administration, in addition to the other hazardous effects associated with this route. Over the last few decades' pharmaceutical scientists throughout the world are trying to explore transdermal and transmucosal routes as an alternative to injections. Among the various transmucosal sites available, mucosa of the buccal cavity was found to be the most convenient and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery as retentive dosage forms, because it has expanse of smooth muscle which is relatively immobile, abundant vascularization, rapid recovery time after exposure to stress and the near absence of langerhans cells. Direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Further, these dosage forms are self-administrable, cheap and have superior patient compliance. Developing a dosage form with the optimum pharmacokinetics is a promising area for continued research as it is enormously important and intellectually challenging. With the right dosage form design, local environment of the mucosa can be controlled and manipulated in order to optimize the rate of drug dissolution and permeation. A rational approach to dosage form design requires a complete understanding of the physicochemical and biopharmaceutical properties of the drug and excipients. Advances in experimental and computational methodologies will be helpful in shortening the processing time from formulation design to clinical use. This paper aims to review the developments in the buccal adhesive drug delivery systems to provide basic principles to the young scientists, which will be useful to circumvent the difficulties associated with the formulation design.

Adjuvants, Pharmaceutic↗
PubMed2003

Dosing information for paediatric patients: are they really "therapeutic orphans"?

OBJECTIVES: To review the approved product information (PI) of prescription medicines to determine the extent and nature of information available on paediatric dosing and the availability of paediatric dosage formulations in Australia. METHODS: The PIs for all prescription medicines listed in the Australian Monthly Index of Medical Specialties (MIMS) were reviewed. Dosing information for each PI was categorised according to age groupings. PIs claiming suitability for use in paediatric patients were reviewed for information on the availability of paediatric dosage forms. MAIN OUTCOME MEASURES: Proportion of PIs providing paediatric dosing information; availability of dosage forms suitable for children. RESULTS: A total of 1497 PIs were reviewed. The proportions, for each age group, of PIs with inadequate paediatric dosing information were: < 1 month (80.5%), 1-3 months (79.1%), 3 months-2 years (77.5%), 2-6 years (73.2%), and 6-12 years (71.6%). The proportions, for each age group, of PIs that gave specific paediatric dosing information but did not provide a paediatric dosage form were: < 1 month (26.5%), 1-3 months (25.1%), 3 months-2 years (23.3%), 2-6 years (21.9%), and 6-12 years (24.0%). CONCLUSIONS: The PIs for many prescription products listed in MIMS do not adequately detail paediatric doses. Many medicines for which specific paediatric dosing information is given are not available in dosage forms appropriate for children.

Australia↗
PubMedDate not supplied

Rectal versus oral absorption of codeine phosphate in man.

Rectal absorption of codeine phosphate from various dosage forms was studied in man. The rectal dosage forms included aqueous solutions and fatty suppositories. A comparison was made with an orally administered solution. The plasma concentrations of codeine were measured by means of HPLC analysis after a single dose of 60 mg codeine phosphate in a cross-over study in 7 volunteers. Compared with oral dosing rectal absorption from an aqueous solution or a fatty suppository produced an almost identical plasma concentration profile with similar interindividual variations. Comparing the absorption rate characteristics it appeared that rectal absorption from an alkaline solution containing codeine phosphate proceeded significantly (P less than 0.05) more rapid than after oral dosing. No essential difference in bioavailability was observed between the various rectal and oral dosage forms.

Administration, Oral↗
PubMed1987

Correlation of ibuprofen bioavailability with gastrointestinal transit by scintigraphic monitoring of 171Er-labeled sustained-release tablets.

External gamma scintigraphy was used to monitor the gastrointestinal (GI) transit of radiolabeled sustained-release tablets containing 800 mg ibuprofen in eight fasted healthy volunteers. Ibuprofen serum concentrations were determined from blood samples drawn sequentially over a 24-hr period. Serum concentrations and related parameters were correlated to the position of the dosage form in the GI tract from the scintiphotos. The sustained-release tablets were radiolabeled intact utilizing a neutron activation procedure, by incorporating 0.18% of 170Er2O3 (enriched to greater than 96% 170Er) into the bulk formulation. After manufacture of the final dosage forms, the tablets were irradiated in a neutron flux (4.4 x 10(13) n/cm2.sec) for 2 min, converting the stable 170Er to radioactive 171Er (t1/2 = 7.5 hr). Each tablet contained 50 microCi of 171Er at the time of administration. The scintigraphy studies suggested that the greatest proportion of ibuprofen was absorbed from this dosage form while the tablet was in the large bowel. The dosage forms eroded slowly in the small bowel and appeared to lose their integrity in the large bowel. In vitro studies showed only minimal effects of the neutron irradiation procedure on the dosage form performance.

Biological Availability↗
PubMed2000

Second derivative ultraviolet spectrophotometry and HPTLC for the simultaneous determination of vitamin C and dipyrone.

Two accurate, precise and sensitive thin layer chromatographic (TLC) and second derivative UV-spectrophotometric procedures are described for the simultaneous determination of ascorbic acid and dipyrone in pure form and in pharmaceutical dosage forms. The TLC method involved direct application of methanolic solutions of tested samples on silica gel TLC plates using water:methanol (95:5 v/v) as developing system. The developed plates were then directly scanned at 260 nm using a TLC scanner. The second method depends on second derivative UV-spectrophotometry with zero crossing technique of measurement. Second derivative amplitudes at 280 and 272 nm were selected for the determination of ascorbic acid and dipyrone, respectively. Both methods show good linearity, precision and reproducibility. They are simple and do not require manipulation prior to analysis. The proposed methods have been successfully applied to the determination of the drugs in various pharmaceutical dosage forms such as tablets and ampoules.

Ascorbic Acid↗
PubMed2006

Spectrophotometric determination of trazodone, amineptine and amitriptyline hydrochlorides through ion-pair formation with molybdenum and thiocyanate.

Extraction spectrophotometric method has been developed for the determination of tricyclic drugs such as trazodone (TZH), amineptine (APH) and amitriptyline (ATPH) hydrochlorides in pure form and in the dosage forms coming from different Egyptian markets. The method based on the formation of ion-pairs between these drugs under investigation and inorganic complex of Mo(V)-thiocyanate followed by its extraction with methylene chloride. The optimum conditions for the ion-pairs formation are established. The method permits the determination of TZH, APH and ATPH over the concentration range of 2-28, 2-32 and 1-30 microg ml(-1), respectively. The Sandell sensitivity (S) is found to be 0.105, 0.138 and 0.118 g cm(-2) for TZH, APH and ATPH, respectively. The SD is found to be 0.16-0.377, 0.12-0.259 and 0.091-0.286 and the R.S.D. are 0.14-0.55, 0.12-0.399 and 0.095-0.485 for TZH, APH and ATPH, respectively. The method is applicable for the assay of the investigated drugs in different dosage forms and the results are in good agreement with those obtained by the official method.

Absorption↗
PubMed2006

Spectrophotometric determination of trazodone, amineptine and amitriptyline hydrochlorides through ion-pair formation using methyl orange and bromocresol green reagents.

A simple and rapid extraction spectrophotometric procedure has been developed for the determination of tricyclic anti-depressant drugs such as trazodone (TZH), amineptine (APH) and amitriptyline (ATPH) hydrochlorides in pure form and in different dosage forms. The method involves the formation of intense yellow ion-pairs between these drugs under investigation and methyl orange (MO) and bromocresol green (BCG) reagents followed by their extraction with 1,2-dichloroethane and quantitative microdetermination at 420 and 410 nm using MO or BCG, respectively. The optimum experimental conditions for the ion-pairs formation are established. The method permits the determination of TZH, APH and ATPH over a concentration range of 2-50, 2-50 and 1-25 microg ml(-1) for TZH, APH and ATPH, using MO and 1-25 microg ml(-1) for TZH, APH and ATPH, using BCG, respectively. The Sandell sensitivity (S) is found to be 0.106, 0.1071 and 0.0907 g cm(-2) for TZH, APH and ATPH, respectively, using MO reagent and 0.0788, 0.0661 and 0.0494 g cm(-2) for TZH, APH and ATPH, respectively, using BCG. The method is applicable for the assay of the investigated drugs in different dosage forms and the results are in good agreement with those obtained by the official method.

Amitriptyline↗
PubMed1995

Rational use of oral antibiotics for pediatric infections.

We carried out a survey in Japan to investigate compliance among children given oral antibiotics in an outpatient setting. The results of our survey revealed that, in Japan, approximately one-quarter of patients did not take their full course of antibiotics. Reasons for unsupervised self-discontinuation included: (1) the parent or guardian judged the infection to be cured; (2) the child refused to take the drug; and (3) the appearance of side effects. Causative organisms often involved in respiratory infections experienced in out-patient medicine include pneumococci, streptococci, staphylococci, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and Mycoplasma pneumoniae. The beta-lactams are effective against all of these bacterial species, with the exception of M. pneumoniae. We conducted a survey of beta-lactam antibiotics currently on the Japanese market and compared them to other oral antibiotics used to treat respiratory infections. Ease of administration, based on the incidence of adverse effects, particularly diarrhea, the dosage form, taste, dosage per administration and the number of doses required per day, are reported.

Administration, Oral↗
PubMed2006

Generic substitution: the use of medicinal products containing different salts and implications for safety and efficacy.

In their quest to gain early entry of new generic products into the market prior to patent expiration, one of the strategies pursued by generic drug product manufacturers is to incorporate different salts of an approved active pharmaceutical ingredient (API) in a brand company's marketed dosage form and subject such dosage forms to bioequivalence assessment. These initiatives present challenges to regulatory authorities where the decision to approve bioequivalent products containing such pharmaceutical alternatives must be considered in the light of safety and efficacy, and more particularly, with respect to their substitutability. This article describes the various issues and contentions associated with the concept of pharmaceutical alternatives, specifically with respect to the uses of different salts and the implications for safety, efficacy and generic substitution.

Animals↗
PubMedDate not supplied

Pharmacokinetic-pharmacodynamic modeling: why?

At present, pharmacokinetic-pharmacodynamic (PK-PD) modeling has emerged as a major tool in clinical pharmacology to optimize drug use by designing rational dosage forms and dosage regimes. Quantitative representation of the dose-concentration-response relationship should provide information for prediction of the level of response to a certain level of drug dose. Several mathematical approaches can be used to describe such relationships, depending on the single dose or the steady-state measurements carried out. With concentration and response data on-phase, basic models such as fixed-effect, linear, log-linear, E(MAX), and sigmoid E(MAX) can be sufficient. However, time-variant pharmacodynamic models (effect compartment, acute tolerance, sensitization, and indirect responses) can be required when kinetics and response are out-of-phase. To date, methodologies available for PK-PD analysis barely suppose the use of powerful computing resources. Some of these algorithms are able to generate individual estimates of parameters based on population analysis and Bayesian forecasting. Notwithstanding, attention must be paid to avoid overinterpreted data from mathematical models, so that reliability and clinical significance of estimated parameters will be valuable when underlying physiologic processes (disease, age, gender, etc.) are considered.

Algorithms↗