Biomedical subjects

T Bussemer

Publications and source records attributed to T Bussemer.

6 recordsLinked to original sources

PubMed2004

Process and formulation variables affecting the performance of a rupturable capsule-based drug delivery system with pulsatile drug release.

The objective of this study was to optimize several process and formulation parameters, which influence the performance of a rupturable, pulsatile drug delivery system. The system consisted of a drug-containing hard gelatin capsule, a swelling layer of croscarmellose (Ac-Di-Sol) and a binder, and an outer ethylcellulose coating. Polyvinyl pyrrolidone (Kollidon 90F) was superior to HPMC and HPC as a binder for the swelling layer with regard to binding (adherence to capsule) and disintegration properties of the swelling layer. The capsule-to-capsule uniformity in the amount of swelling layer and outer ethylcellulose coating, which significantly affected the lag time prior to rupture of the capsule, was optimized by decreasing the batch size, and by increasing the rotational pan speed and the distance between the spray nozzle and the product bed. The type of baffles used in the coating pan also affected the layering uniformity. Fully-filled hard gelatin capsules had a shorter lag time with a higher reproducibility compared to only half-filled capsules, because the swelling pressure was directed primarily to the outer ethylcellulose coating and not to the inner capsule core. Stability studies revealed that the lag time of the capsules was stable over a 240-day period when the moisture content was kept unchanged.

Capsules↗

PubMed2003

A pulsatile drug delivery system based on rupturable coated hard gelatin capsules.

The objective of this study was to develop and evaluate a pulsatile drug delivery system based on drug-containing hard gelatin capsules, which were coated with a swelling layer and an outer insoluble, water-permeable polymeric coating. An inner pressure developed by the swelling layer resulted in the rupture of the outer coating. Preliminary studies with a simulated rupture test demonstrated the dependence of the lag time prior to rupture on the properties of the coating, such as its water permeability and mechanical strength. The lag time increased with a higher coating level, but decreased with the addition of the hydrophilic pore former, hydroxypropyl methylcellulose. Increasing the amount of the swelling layer decreased the lag time. The coated capsules took up release medium at a nearly constant rate until a critical maximum was reached, where the swelling pressure was sufficient to rupture the outer coating. The rate of medium uptake decreased with increasing coating level, while the extent of medium uptake was almost the same for the different coating levels. A hydrophobic particulate material, magnesium stearate, was added to the coating layer to reduce the mechanical strength and therefore the lag time. The test conditions, such as surfactant addition to the release medium or floating vs. complete immersion of capsules in the medium, affected the lag time.

Capsules↗

PubMed2003

Formulation parameters affecting the performance of coated gelatin capsules with pulsatile release profiles.

The objective of this study was to develop and evaluate a rupturable pulsatile drug delivery system based on soft gelatin capsules with or without a swelling layer and an external water-insoluble but -permeable polymer coating, which released the drug after a lag time (rupturing of the external polymer coating). The swelling of the gelatin capsule itself was insufficient to rupture the external polymer coating, an additional swelling layer was applied between the capsule and the polymer coating. Croscarmellose sodium (Ac-Di-Sol) was more effective as a swelling agent than low and high molecular weight hydroxypropylmethyl cellulose (HPMC; E5 or K100M). Brittle polymers, such as ethyl cellulose (EC) and cellulose acetate propionate (CAPr), led to a better rupturing and therefore more complete drug release than the flexible polymer coating, Eudragit RS. The lag time of the release system increased with higher polymer coating levels and decreased with the addition of a hydrophilic pore-former, HPMC E5 and also with an increasing amount of the intermediate swelling layer. The water uptake of the capsules was linear until rupture and was higher with CAPr than with EC. Soft gelatin capsule-based systems showed shorter lag times compared to hard gelatin capsules because of the higher hardness/filling state of the soft gelatin capsules. The swelling pressure was therefore more directed to the external polymer coating with the soft gelatin capsules. Typical pulsatile drug release profiles were obtained at lower polymer coating levels, while the release was slower and incomplete at the higher coating levels. CAPr-coated capsules resulted in a more complete release than EC-coated capsules.

Capsules↗

PubMed2003

Evaluation of the swelling, hydration and rupturing properties of the swelling layer of a rupturable pulsatile drug delivery system.

The objective of this study was to investigate the swelling characteristics of various swellable polymers in swelling layers that induce the rupturing of an outer polymer coating in pulsatile drug delivery systems (DDS). An apparatus was designed to measure simultaneously the swelling energy/force and water uptake of discs, made of polymers. The swelling energy of several excipients decreased in the following order: croscarmellose sodium (Ac-Di-Sol) > low-substituted hydroxypropyl cellulose (L-HPC) > sodium starch glycolate (Explotab) > crospovidone (Kollidon CL) > hydroxypropyl methylcellulose (Methocel K100M). A linear correlation existed between the swelling energy and the water uptake. The swelling behavior of Ac-Di-Sol depended on the ionic strength and the pH of the medium due to a competition for free water and the acidic nature of this polymer. Analysis of the time-dependent swelling force data with a previously developed exponential equation confirmed a diffusion-controlled swelling force development, predominantly controlled by the penetration rate of the medium. The swelling behavior and the rupture of the outer polymeric coating of a pulsatile DDS were demonstrated in simulation tests.

Capsules↗

PubMed2003

Time-dependent mechanical properties of polymeric coatings used in rupturable pulsatile release dosage forms.

The mechanical properties of polymer films used in pharmaceutical coatings of pulsatile drug delivery systems were evaluated in the dry and the wet state by a newly developed puncture test, which allowed the time-dependent measurement of the mechanical properties on the same film specimen. Force, puncture strength, energy at break, modulus, and strain were investigated as a function of water exposure time with respect to the type of polymer and the type and concentration of plasticizer and pore former (hydroxypropyl methylcellulose, HPMC). Eudragit RS films were very flexible, had a high strain, and broke upon puncture with only small cracks. In contrast, ethylcellulose films were more brittle with a lower strain and showed complete film rupture. Increased amounts of the hydrophilic pore former, HPMC, resulted in a reduced puncture strength and in an increase in water uptake and weight loss of the films. The puncture strength decreased with increasing plasticizer concentration and was lower with the lipophilic dibutyl sebacate than with the hydrophilic triethyl citrate.

Acrylic Resins↗

PubMed2001

Pulsatile drug-delivery systems.

Delivery systems with a pulsatile-release pattern are receiving increasing interest for the development of drugs for which conventional controlled drug-release systems with a continuous release are not ideal. These drugs often have a high first-pass effect or special chronopharmacological needs. A pulsatile-release profile is characterized by a time period of no release (lag time) followed by a rapid and complete drug release. Pulsatile drug-delivery systems can be classified into site-specific systems in which the drug is released at the desired site within the intestinal tract (e.g., the colon), or time-controlled devices in which the drug is released after a well-defined time period. Site-controlled release is usually controlled by environmental factors, like the pH or enzymes present in the intestinal tract, whereas the drug release from time-controlled systems is controlled primarily by the delivery system and, ideally, not by the environment. This review covers various single- and multiple-unit oral pulsatile drug-delivery systems with an emphasis on time-controlled drug-release systems.

Administration, Oral↗