Thein vitro development of extended-release solid oral dosage forms

Leeson, Lewis J.; Adair, Dennis; Clevenger, James; Chiang, Nora

doi:10.1007/bf01059332

Cited by 22 publications

(3 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The technique was first tested by retrospectively describing plasma concentration data for several commercial controlled-release products (13). No attempt was made to isolate the influence of the k a value on the success of the products.…”

Section: Evaluation Of Absorption Rate Constants In Previously Reportmentioning

confidence: 99%

A Nomogram to Evaluate Intrinsic Absorption Rate Constants of Potential Oral Prolonged-Release Candidates

1999

Pharmaceutical Development and Technology

View full text Add to dashboard Cite

The purpose of this study was to devise a simple method to determine whether or not a drug's absorption rate constant favored the selection of that drug for an oral prolonged-release drug delivery system (DDS). Computer simulations were used to observe the drug time-course in the DDS, the gastrointestinal tract, and the cumulative amount absorbed following administration of an 8-, 12-, and 24-hr zero-order DDS. For each DDS, the drug's intrinsic absorption rate constant, ka, was systematically varied from 0.1 to 10 hr-1. Results demonstrated that the DDS controlled the absorption rate whenever drug release was rate-limiting. However, the release rate did not determine the length of time that a DDS controlled the absorption rate. Instead, the duration of DDS-controlled absorption increased as the ka value increased. When ka > or = 2 hr-1, the DDS controlled more than 80% of the 8-, 12-, and 24-hr dosing intervals. Conversely, when ka < or = 0.12 hr-1, the DDS failed to control absorption. In conclusion, this investigation developed a technique to ascertain the rate-limiting step when a zero-order DDS releases a drug that undergoes first-order absorption. This technique was employed to construct a nomogram that allows its users to estimate the duration of control by an 8-, 12-, or 24-hr DDS based on the ka value for the drug.

show abstract

Section: Evaluation Of Absorption Rate Constants In Previously Reportmentioning

confidence: 99%

A Nomogram to Evaluate Intrinsic Absorption Rate Constants of Potential Oral Prolonged-Release Candidates

1999

Pharmaceutical Development and Technology

View full text Add to dashboard Cite

show abstract

“…Parameters in the models were estimated by minimizing the sum of squared residuals. Plotting the log of cumulative amount undissolved as a function of time, 28) it can be seen in Fig. 5 that the release of metoclopramide from Orgasol matrix tablets could be defined by a biphasic function, and in all cases it appears that there are two releasing fractions, each releasing the drug exponentially, with one fraction releasing more rapidly than the other.…”

Section: Fig 1 Ph Profiles Of Dissolution Medium As a Function Of Tmentioning

confidence: 99%

In Vitro Release of Metoclopramide from Hydrophobic Matrix Tablets. Influence of Hydrodynamic Conditions on Kinetic Release Parameters.

et al. 2001

View full text Add to dashboard Cite

Sustained or controlled-release delivery systems can achieve predictable and reproducible release rates, extended duration of activity for short half-life drugs, decreased toxicity, reduction of required dose, optimized therapy, and better patient compliance. 1,2) With the aim of maximizing the bioavailability of conventional drugs with minimum side effects, new drug delivery systems continue to attract much attention. 3)Matrix-type controlled-delivery systems are popular because of their ease of manufacture. The simple preparation technique involves the compression of a blend of drug and polymer powder by conventional pharmaceutical methods to form disks or tablets. In inert matrix systems, which are also referred to as "monolithic" systems, the active agent is dissolved or dispersed in an inert diffusion barrier. The drug is mixed with an inert polymer that does not interact with biological fluids. Inert matrices should be insoluble and remain intact during the experiment. Drug release is controlled by the polymer properties and structure. [4][5][6][7] The materials used in the preparation of inert matrices are predominantly hydrophobic polymers. Several studies have dealt with the application of polymers such us polyvinylchloride, polyethylene, ethyl cellulose, acrylic resins, and polyamides. [8][9][10][11] Study of the toxicological, physicochemical, and pharmacotechnical properties of polyamide 12 have indicated that it is a nontoxic inert polymer with good characteristics for the production of tablets by the direct compression method. In previous reports we have confirmed slow drug release of compressed tablets with polyamide 12 in the composition. 12-15)The present study reports the use of polyamide 12 (Orgasol) as a new pharmaceutical vehicle in the design of solid controlled-release dosage forms. Inert polyamide 12 (empirical formula -NH-[CH 2 ] 11 -CO-) is obtained by polycondensation of aminolauric acid. Due to the hydrophobic and inert nature of Orgasol and its good fluidity and cohesion, 16) this polymer is a priori suitable for elaborate inert matrix systems. Metoclopramide hydrochloride was chosen as a model drug with high aqueous solubility, because of its pharmacokinetic properties of variable bioavailability (50%), short plasma half-life, and therapeutic interest. It is recommended for use as a potent antiemetic agent in various types of vomiting 17) (e.g., it is the antiemetic of choice for chemotherapyinduced emesis). Metoclopramide is a procainamide derivate with effects based on at least two mechanisms: first it acts in the central nervous system as an antagonist at D2 dopamine receptors; and second, metoclopramide has an agonistic effect on the cholinergic systems in the stomach and gut.18) The result is improved gastroduodenal coordination. High doses of metoclopramide inhibit the effects of serotonergic (5-HT 3 ) receptors on neurons in the gut, in addition to the effect of dopaminergic D 2 receptors at lower doses. Because the activity of metoclopramide is dose dependent, it is importan...

show abstract

“…Biorelevant in vitro testing may be close to in vivo conditions in the case of IR dosage forms. For ER dosage forms, it may reflect the rate and amount by which the active moiety is absorbed from the dosage form, that is, its bioavailability (24). According to Johannes Krämer (PHAST GmbH, Germany), biorelevance may have different meanings depending on whether the API is for local or systemic application and whether the drug release follows a stochastic process or is governed by a rate-controlling mechanism.…”

Section: Contract Research Oranizations Specialized In Ipdmentioning

confidence: 99%