Multiple-unit Tablets Research Articles

İZOSORBİD DİNİTRATIN MODİFİYE SALIM YAPAN ÇOK BİRİMLİ BİLEŞİMİNİN TABLET ŞEKLİNDE BASILMASI VE DEĞERLENDİRİLMESİ

Objective: This study was aimed to create a multiple-unit dosage form of isosorbide dinitrate by pressing spherical matrix granules into tablets, selecting the optimal technology parameters and evaluating the obtained tablets. Material and Method: The tablet cores were prepared from mixtures of active matrix granules and shock-absorbing auxiliary granules in various ratios using diverse tabletting forces. The dissolution profiles of the obtained tablet compositions were evaluated in comparison with the reference preparation. Result and Discussion: An optimal ratio of spheroids with the active component with auxiliary granules along with optimal compression parameters were determined. The resulting as multiple-unit tablets exhibited a release profile similar to that of Cardicket Retard. Used technological approach makes it possible to regulate the dissolution profile of tablets by changing the ratio of active granules with different kinetics of the active substance release.

Prolonged release from orodispersible films by incorporation of diclofenac-loaded micropellets

Prolonged drug release provided by multiple-unit dosage forms is highly beneficial to enhance the compliance and safety of the pharmacotherapy even for patients with swallowing deficiencies. To facilitate the intake for these patients, multiple-unit tablets and capsules have to be crushed or opened. An attempt to overcome these issues has been made by the introduction of orodispersible films (ODFs), which rapidly disintegrate within the oral cavity and facilitate the intake of oral solid dosage forms. The aim of this study was to develop a rapidly disintegrating ODF with prolonged release properties by incorporation of small-sized micropellets (MPs). MPs with a drug load of 70% were produced by wet extrusion and spheronization using Vivapur® MCG as pelletizing aid and diclofenac sodium (DS) as model drug. MPs were film-coated with an Eudragit® RS/RL coating and incorporated into the ODF-forming hypromellose solution. ODFs were produced by solvent casting technique. Disintegration times were determined using the PharmaTest® disintegration tester equipped with sample holders for ODFs. Dissolution studies were performed for MPs and ODFs. X-ray micro-computed tomography was used to visualize internal and external surface structures of MPs before and after release studies. MP-loaded ODFs show fast disintegration within 30 s, whereby film-coated MPs remain intact. Uncoated MPs are disintegrating thus revealing immediate DS release. In comparison, DS release was prolonged for film-coated MPs and corresponding ODFs. Incorporation of different amounts of MPs had no effect on the dissolution, but on mechanical properties of ODFs, which decrease with increasing amounts of MPs.The production of rapidly disintegrating ODFs with prolonged release properties for DS, representing a freely water-soluble drug, was feasible.

Structural changes of polymer-coated microgranules and excipients on tableting investigated by microtomography using synchrotron X-ray radiation

Multiple-unit tablets consisting of polymer-coated microgranules and excipients have a number of advantageous pharmaceutical properties. Polymer-coated microgranules are known to often lose their functionality because of damage to the polymer coating caused by tableting, and the mechanism of polymer coating damage as well as the structural changes of excipients upon tableting had been investigated but without in-situ visualization and quantitative analysis. To elucidate the mechanism of coating damage, the internal structures of multiple-unit tablets were investigated by X-ray computed microtomography using synchrotron X-rays. Cross sectional images of the tablets with sub-micron spatial resolution clearly revealed that void spaces remained around the compressed excipient particles in the tablets containing an excipient composed of cellulose and lactose (Cellactose® 80), whereas much smaller void spaces remained in the tablets containing an excipient made of sorbitol (Parteck® SI 150). The relationships between the void spaces and the physical properties of the tablets such as hardness and disintegration were investigated. Damage to the polymer coating in tablets was found mainly where polymer-coated microgranules were in direct contact with each other in both types of tablets, which could be attributed to the difference in hardness of excipient particles and the core of the polymer-coated microgranules.

Development and Evaluation of a Novel Modified-Release Pellet-Based Tablet System for the Delivery of Loratadine and Pseudoephedrine Hydrochloride as Model Drugs

Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion-spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.

The use of extragranular disintegrants in multiple-unit tablet formulations: effect on compressibility, compactibility and disintegration

Multiple-unit tablets formed from mixtures of microcrystalline cellulose pellets and disintegrants (Ac-Di-Sol, Primojel or Kollidon CL) by compaction were investigated with the aim of controlling tablet tensile strength and disintegration time. The effects of pellet porosity, compaction pressure, and type and amount of disintegrant were studied. Primojel made the pellets less prone to deformation during compression, while the other two disintegrants had very minor effects on the compression behavior. Ac-Di-Sol and Primojel generally increased the tablet tensile strength, whereas the effect of Kollidon CL was dependent on the initial pellet porosity. Kollidon CL was found to significantly reduce the disintegration time, but the other two disintegrants had variable efficacy, and for the low-porosity pellets significantly increased the disintegration time. These results are interpreted as resulting from the interplay between the mechanical characteristics of the pellets and the mechanisms of action of the disintegrants.

Citric acid as excipient in multiple-unit enteric-coated tablets for targeting drugs on the colon

Delivery of drugs to the large bowel has been extensively investigated during the last decade. The aim of this study was to investigate whether enteric-coated tablets could be made from enteric-coated matrix granules and drug release targeted to the colon. Whether in vitro drug release rate and in vivo absorption could be delayed by adding citric acid to the granules and/or to the tablet matrix was also studied. Ibuprofen was used as model drug because it is absorbed throughout the gastrointestinal tract. Eudragit™ S and Aqoat™ AS-HF were used as enteric polymers. Drug release rates were studied at different pH levels and drug absorption was studied in bioavailability tests. The conclusion was that citric acid retarded in vitro drug release when used in multiple-unit tablets. In vivo absorption of ibuprofen was markedly delayed when citric acid was included in both granules and tablet matrix. Further studies are needed to determine the optimal amount of citric acid in formulations.

Development of disintegrating multiple-unit tablets on a high-speed rotary tablet press

Enteric coated bisacodyl pellets were compressed into divisible disintegrating tablets on a high speed rotary tablet press and investigated for pellet damages. The degree of pellet damages was examined via the bisacodyl dissolution during the acid treatment of' the drug release test for enteric coated articles according to USP 23. The damages depended on the type of filler-binder used and settings of the tablet press. Avicel PH 101 proved to be the most suitable filler-binder, effecting homogeneous distribution of the pellets within the tablets, as could be shown by image analysis of coloured pellets. The speed of the tablet press had noo influence on the pellet damages using Avicel PH 101 as a filler-binder, however, tablets containing 70% (w/w) of coated pellets did not fulfil the requirements of USP 23, despite optimum elasticity and coating thickness of a new Eudragit FS 30 D coating. Reducing the proportion of pellets to 60% per tablet, less than 10% of bisacodyl were released within 2 h during acid treatment thus fulfilling the requirements of the USP 23.

Study of in Vitro Kinetics and Liberation Mechanism of Pentoxifylline from Coated Pellets and Compacts Based on 2-Hydroxyethylmethacrylate-Butyl Acrylate Copolymer

AbstractThe influence of certain polymerous auxiliary materials upon the liberation kinetics and mechanism of pentoxifylline from peroral dosage forms has been followed. Solutions in organic solvents (R1, R2, R3) and water dispersions (E35, E36, E37) of the 2-hydroxyethyl methacrylate -butylacrylate (2-HEMA-BuA) copolymer containing the monomers as shown in various ratios, were being evaluated. Pellets were prepared from pentoxifylline coated by a layer of the polymers studied, with the subsequent production (by means of direct compression) of tablets containing 300 mg of the drug each. Release of pentoxifylline from the coated pellets and tablets has been determined by the dissolution test in accordance with the 4th edition of the Czechoslovak Pharmacopoeia. Using the Weibull and Higuchi functions parameters, the retarding ability of individual polymers was evaluated. Two mechanisms, viz. the formation of multiple unit tablets from coated pellets, and the application of a suitable polymer type, were obse...