Addition Of Disintegrants Research Articles

Immediate-Release Formulations Produced via Twin-Screw Melt Granulation: Systematic Evaluation of the Addition of Disintegrants

The current study evaluated the effect of location and amount of various superdisintegrants on the properties of tablets made by twin-screw melt granulation (TSMG). Sodium-croscarmellose (CCS), crospovidone (CPV), and sodium starch glycolate (SSG) were used in various proportions intra- and extra-granular. Tabletability, compactibility, compressibility as well as friability, disintegration, and dissolution performance were assessed. The extra-granular addition resulted in the fasted disintegration and dissolution. CPV performed superior to CCS and SSG. Even if the solid fraction (SF) of the granules was lower for CPV, only a minor decrease in tabletability was observed, due to the high plastic deformation of the melt granules. The intra-granular addition of CPV resulted in a more prolonged dissolution profile, which could be correlated to a loss in porosity during tableting. The 100% intra-granular addition of the CPV resulted in a distinct decrease of the disintegration efficiency, whereas the performance of SSG was unaffected by the granulation process. CCS was not suitable to be used for the production of an immediate-release formulation, when added in total proportion into the granulation phase, but its efficiency was less impaired compared to CPV. Shortest disintegration (78 s) and dissolution (Q80: 4.2 min) was achieved with CPV extra-granular. Using CPV and CCS intra-granular resulted in increased disintegration time and Q80. However, at a higher level of appx. 500 s and appx. 15 min, only SSG showed a process and location independent disintegration and dissolution performance.

English

English

СУЧАСНИЙ СТАН СТВОРЕННЯ, ВИРОБНИЦТВА ТА ДОСЛІДЖЕННЯ ТАБЛЕТОВАНИХ ЛІКАРСЬКИХ ПРЕПАРАТІВ. Повідомлення 18. Особливості застосування та характеристика дезінтеграторів при виробництві таблеток

<p align="center">MODERN STATE OFCREATION, PRODUCTION AND RESEARCH OF TABLET DRUGS</p><p align="center">М. А. Ezhned<sup>1</sup> , О. V. Тryhubchak<sup>2</sup> , Т. А. Hroshovyi<sup>2</sup></p><p><sup>1</sup>BukovynianStateMedicalUniversity</p><p><sup>2</sup>Ternopil State Medical University byI. Ya. Horbachevsky</p><p><strong>Summary:</strong> the literature date about action mechanisms, introduction methods аnd physico-chemical proporties of desintegrators are presented. Examples are given for characteristics of leavens impact for slacking time of tablets.</p><p><strong>Key words:</strong> tablets, excipients, desintegrators, leavens, slacking, intumescense.</p><p><strong>Introduction</strong>. In the pharmaceutical market for more than three quarters of the total volume of finished drugs are taken by tablets. They can be used both for acute and chronic conditions, they are convenient to use. This explains the widespread tablets worldwide. In recent years, increasing attention has been paid to the development of fast dissolving tablets and / or disintegration that could easily swallow and tablets intended for dissolution and / or rapid disintegration in the oral cavity.</p><p>To improve the disintegration or dissolution of the tablets used in the manufacture of digging substances that provide mechanical destruction tablets in a liquid medium. Rippers added into the tablets also if the drug is insoluble in water or if the tablet is capable of self cemented during storage.</p><p>According to the requirements of good manufacturing practice disintegrants must meet the following requirements: negligible solubility, slight gel formation, good ability to hydration, good forming properties and flowability properties, no interaction with drugs.</p><p><strong> </strong></p><p><strong>Results and disussion.</strong></p><p>According to the literature, depending on the method of administration and the physicochemical properties of disintegrators there are several mechanisms by which tablets disintegrate into small pieces, and then form a homogeneous suspension.</p><p>One of them involves capillary effect in which water accumulates within the matrix tablets, breaking the link between matrix and particles contributing to the disintegration of tablets. When disintegrant transport water into the matrix tablets, all soluble particles are dissolved, leading to a rapid disintegration of the tablet.</p><p>According to the views of other authors, not all Rippers swell with water. Swelling, nevertheless, consider the starting point at which certain disintegrants (such as starch) cause disintegration of tablets. When swelling into contact with water, adhesiveness other ingredients in the tablet is overcome, which also leads to the disintegration of the tablet.</p><p>Another mechanism caused the collapse of tablets include citric or tartaric acid with sodium bicarbonate, sodium carbonate, potassium bicarbonate or calcium carbonate. Thus in contact with water is released carbon dioxide, which breaks tablet.</p><p><strong>Conclusion</strong>. So, swelling pure ripper better correlated with swelling substances and mixtures of tablet efficiency of these materials which significantly increases the dissolution of the drug. Dissolution of the drug encapsulated dosage form can be significantly improved with the addition of disintegrants in the composition. The effectiveness of baking powder used depends on the nature of the filler and lubricating agents. The collapse of the tablets thus depends on the type and amount of baking powder. Thus, the disintegration of tablets attracted considerable attention as an important step in obtaining tablets with rapid release of the drug.<strong></strong></p>

Design of rapidly disintegrating drug delivery films for oral doses with hydoxypropyl methylcellulose

The purpose of this study was to develop pharmaceutical thin films that disintegrate rapidly in the oral cavity. Films containing acetaminophen as a model drug were prepared by the solution/solvent casting method. HPMC as a polymeric film former, MCC and pregelatinized starch as disintegrants, and micronized L-HPC as both a film former and a disintegrant were examined. The disintegration time and the tensile strength were measured. The surface morphologies of the films were compared using SEM. The addition of disintegrants or especially the optimal content of L-HPC into the films shortened the disintegration time and affected the tensile strength.

Sustained-release effect of codried excipients of microcrystalline cellulose and Ganoderma fiber

The sustained-release effects of codried excipient of modified Ganoderma (treated with alkaline solution) and microcrystalline cellulose at different ratios were examined using acetaminophen (ACT) as a model drug. Results demonstrate that the crushing strength of most ACT tablets made with codried powder at all ratios increased as compaction force increased; but a rapid decline was observed when compression force exceeded 2 tons. Drug release from tablets compressed at 0.5 ton increased as modified Ganoderma fiber content increased. But when the compression force exceeded 1 ton, the release rate was not influenced by the compaction force or the increasing content of Ganoderma fiber. However, the dissolution of ACT from these tablets could be sustained for longer than 24 h. The extent of drug release was shown to increase with increasing amounts of modified Ganoderma in the codried excipient. The addition of disintegrants could further accelerate the drug release from the tablet. Drug release was also dependent upon the amount and kind of disintegrant used. The influence was in the following order: primojel>crospovidone>starch 1500.

Development of an abdominal magnetic resonance (MR) contrast agent formulation with Oral Magnetic Particles (OMP, Ferristene)

A formulation for fast dispersible granules with the magnetic resonance (MR) contrast agent, Oral Magnetic Particles (OMP), was developed. The formulation contained viscosity-increasing agents (xanthan gum and a mixture of microcrystalline cellulose and sodium carboxymethylcellulose). The granules were dispersed easily in water when stirred by hand and became a viscous OMP suspension with apparent homogeneity, but does not form granule aggregates (lump), within 10 min. The dispersibility was greatly affected by the binder type and addition of disintegrant. Hydroxypropylcellulose and low-substituted hydroxypropylcellulose were preferable. The preparation method to incorporate OMP into the granules also greatly influenced the dispersibility of the granules. A fluidized bed granulation of the base granules containing additives and subsequent coating of OMP onto the granules was eventually utilized. The formulation was able to control the viscosity of the suspension by regulating the content of viscosity-increasing agent while maintaining dispersibility. The developed formulation gave a good MR contrast image in rats and no magnetic susceptibility artifact was observed.

Reducing dust and improving granule and tablet quality in the roller compaction process

The dramatic reduction of non-compacted material during roller compaction and an important improvement of the granule and tablet qualities were obtained by a controlled wetting process before the roller compaction. The continuity of the roller compaction process was maintained by using a continuous fluid bed system. Due to a controlled water addition, a better binder distribution was obtained than when using micronised dry binders. When dry compacting poorly water soluble hydrochlorothiazide mixtures, the resultant dissolution rate was not influenced by the HPMC binder viscosity. When moistened blends were compacted, the resultant dissolution rate decreased with increasing HPMC binder viscosity. The roller compaction pressure had almost no influence on the drug dissolution rate. The addition of disintegrants did not improve the dissolution rate. When a fraction of the filler α-lactose monohydrate was replaced by microcrystalline cellulose, the dissolution rate increased with an increasing microcrystalline cellulose fraction. With the addition of 0.5% Tween® 80 to a formulation containing 25% microcrystalline cellulose and 50% α-lactose monohydrate, the dissolution rate increased and an immediate release tablet formulation was obtained. The presence of microcrystalline cellulose also improved the processing and avoided lump formation.

Studies on tableting properties of lactose. VIII. The effect of variations in primary particle size, percentage of amorphous lactose and addition of a disintegrant on the disintegration of spray-dried lactose tablets

Disintegration of tablets compacted from spray-dried lactose samples was found to depend on the amount of amorphous lactose, the size of the primary particles and the compaction load, respectively. The poor disintegration properties of amorphous lactose was explained by pointing to the dissolution characteristics of the substance. Considerable improvement of the disintegration properties can be obtained by addition of suitable disintegrants.

The role of disintegrants in hard-gelatin capsules.

Experiments were designed to investigate the efficacy of various disintegrants on hydrochlorothiazide dissolution from soluble (lactose) and insoluble (dicalcium phosphate) fillers at various lubricant concentrations and compression forces. Capsule fill weights as well as slug hardness appeared to be influenced by the addition of disintegrants. Disintegration times were not always in rank order agreement with dissolution data. Analysis of the dissolution data by 3-way analysis of variance revealed that all the main factors (disintegrant, compression force, lubricant and/or diluent) and their interactions were significant. The presence of interactions limits the conclusions to be drawn; however, an assessment of the averaged effect of each factor separately revealed several important relationships. A compression force effect was evident in most cases at the lower disintegrant concentration, and lower lubricant concentrations or a more soluble filler appeared to require lesser amounts of disintegrant. The magnitude and order of effectiveness of the disintegrants were altered when the filler system was changed from lactose to dicalcium phosphate.

Cation-Decationized y type zeolites as catalysts of petrochemical processes (review): Khr. Dimitrov and Tsv. Bezukhanova, Neftekhimiya 23, No. 4, 454–469, 1983

A formulation for fast dispersible granules with the magnetic resonance (MR) contrast agent, Oral Magnetic Particles (OMP), was developed. The formulation contained viscosity-increasing agents (xanthan gum and a mixture of microcrystalline cellulose and sodium carboxymethylcellulose). The granules were dispersed easily in water when stirred by hand and became a viscous OMP suspension with apparent homogeneity, but does not form granule aggregates (lump), within 10 min. The dispersibility was greatly affected by the binder type and addition of disintegrant. Hydroxypropylcellulose and low-substituted hydroxypropylcellulose were preferable. The preparation method to incorporate OMP into the granules also greatly influenced the dispersibility of the granules. A fluidized bed granulation of the base granules containing additives and subsequent coating of OMP onto the granules was eventually utilized. The formulation was able to control the viscosity of the suspension by regulating the content of viscosity-increasing agent while maintaining dispersibility. The developed formulation gave a good MR contrast image in rats and no magnetic susceptibility artifact was observed.

Mprovement in Pressure-Dependent Dissolution of Trepibutone Tablets by Using Intragranular Disintegrants

AbstractIn developing compressed tablets trepibutone 40mg, dissolution studies indicated that the compression pressure applied exerted strong influence on drug dissolution from the tablets. It was found that the incorporation of disintegrants in the granular formulation prevented the decrease in dissolution rate of drug from tablets by compression. Instead of the intragranular disintegrants, incorporation of a rubber powder, which does not swell at all in water and has some elastic recoveries after compression, did not improve the drug dissolution from tablets. It was concluded that the addition of disintegrants in the granular formulation resulted in little prevention of the particle aggregation during compression. The swelling of disintegrant grains in water is considered to play an important part in the deaggregation of drug particles