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Effervescent tablets containing stiripentol solid dispersion and preparation method thereof

A technology of solid dispersion and stiripentol, which is applied to medical preparations containing active ingredients, dispersion liquid delivery, and pharmaceutical formulations, etc. It can solve problems such as poor material safety, reduced drug permeability, and poor patient compliance , to achieve the effect of improving intestinal permeability, improving solubility, and taking convenience

Active Publication Date: 2021-12-21
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Because stiripentol is easily degraded by gastric acid, resulting in extremely low bioavailability in vivo, the oral absorption fraction is only 0.21%
Therefore, marketed formulations usually require high doses (up to 4 g per day) and must be taken with meals (to avoid being destroyed by gastric acid), resulting in strong side effects and poor patient compliance
The few reports on improving the resistance of STP to gastric acid degradation are to prevent STP from being destroyed by gastric acid in the form of passive encapsulation or sustained release through micelles, nanoemulsions, and protein-stabilized drug nanosuspensions. These systems have synthetic steps for the materials used complex 1 , poor material safety 2 , decreased drug permeability 3 , low drug loading 4 or easily dissociated in physiological solution 3 or gather 4 and other defects

Method used

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  • Effervescent tablets containing stiripentol solid dispersion and preparation method thereof
  • Effervescent tablets containing stiripentol solid dispersion and preparation method thereof
  • Effervescent tablets containing stiripentol solid dispersion and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] Example 1: Recipe optimization and solid-state characterization of solid dispersions

[0078] The preparation process is as figure 1 As shown, the formulation optimization and solid-state characterization are as follows:

[0079] 1) Effect of sieve mesh on dissolution behavior of solid dispersion in gastric juice and intestinal juice

[0080] Accurately weigh 100mg of stiripentol and 400mg of Eudragit L100, dissolve them in 3mL of mixed solvent (ethanol: dichloromethane = 1:1, v / v) successively, dissolve them completely by ultrasonication in a water bath, and then vortex for 2 minute. Organic solvents were removed under vacuum on a rotary evaporator at 45°C, 180 rpm. The obtained dried solid system was stored in a desiccator at room temperature for 24 hours before crushing and sieving, and then it was taken out and pulverized into coarse particles and passed through 60, 80 and 100 mesh screens respectively to obtain solid dispersions of different sizes. For dissolut...

Embodiment 2

[0100] Embodiment 2: the preparation method and prescription screening of effervescent tablet

[0101] 1) Optimization of effervescent tablet preparation method

[0102] For powder direct compression method, at first all auxiliary materials are all passed through 80 mesh sieves respectively, then the anhydrous citric acid of prescription quantity is mixed with direct compression type mannitol for 10 minutes to obtain mixture 1, then the sodium bicarbonate of prescription quantity and The solid dispersion was mixed for 10 minutes to obtain mixture 2, and finally the mixtures 1 and 2 were fully mixed and then compressed into tablets immediately. For dry granulation and tabletting, the flakes obtained by the above-mentioned powder direct compression method are crushed into coarse particles, passed through a 20-mesh sieve for sizing, and immediately pressed into tablets according to the prescribed amount. For wet granulation tableting, first pass all excipients through 80-mesh si...

Embodiment 3

[0116] Embodiment 3: In vivo intestinal perfusion experiment studies the penetration enhancement effect of stiripentol solid dispersion

[0117] 1) Physiological saline: Accurately weigh 9g of NaCl and dissolve it in 1000mL of water.

[0118] 2) Chloral hydrate injection: accurately weigh 3.3 g of chloral hydrate, and dilute to 100 mL with normal saline.

[0119] 3) Krebs-Ringer buffer: 7.8g NaCl, 0.35g KCl, 0.37g CaCl per 1000mL water 2 ,0.22gMgCl 2 ,0.22g NaH 2 PO4, 1.4g C 6 h 12 o 6 ,1.37g NaHCO 3 , adjust the pH of the buffer to 7.4 with phosphoric acid or sodium hydroxide.

[0120] 4) Intestinal perfusate: Accurately weigh an appropriate amount of STP solid dispersion, and use pH 7.4 Krebs-Ringer buffer to prepare a concentration of 100 μg·mL -1 The intestinal perfusate was ultrasonically dissolved for use as the test solution. Accurately weighed 20 mg of STP raw material, and prepared 200 mL of STP suspension solution with pH 7.4 Krebs-Ringer buffer as a control...

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Abstract

The invention belongs to the field of pharmaceutical preparations, and particularly relates to effervescent tablets containing a stiripentol solid dispersion and a preparation method thereof. According to the effervescent tablets disclosed by the invention, in one aspect, an indissolvable drug is prepared into an amorphous solid dispersion, so that the defect that the permeability of gastrointestinal tracts is reduced by other solubilizing means is overcome while the water solubility and the dissolution rate are improved, and the effervescent tablets have relatively high encapsulation efficiency (16.67%-50%); in the other aspect, a common, easily available and safe enteric-coated material is selected as a solid dispersion carrier to ensure that the stiripentol is released in the small intestine in a positioned manner and cannot be dissociated in advance in a physiological solution to cause damage of gastric acid to medicine like other preparation means; and besides, compared with commercially available dosage forms (capsules and dry suspensions), the effervescent tablets overcome the problem that the content is easy to cake, and has the advantages of stable storage, convenience in taking, good taste, particular suitability for epilepsy children who cannot swallow solid preparations, and the like.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, in particular to an effervescent tablet containing stiripentol solid dispersion and a preparation method thereof. Background technique [0002] Stipopentol (STP) belongs to BCS Ⅱ drugs with low water solubility and high permeability, and its slow and incomplete dissolution in the gastrointestinal tract is the rate-limiting step of its oral absorption. Commonly used methods to increase the apparent solubility of drugs include generating soluble salts, changing crystal forms / solvates, co-crystals, solubilizing surfactants, using latent solvents / solvents, forming clathrates or nanoscale delivery systems, etc. However, while these methods increase the solubility of the drug, the permeability of the drug will be reduced, thereby affecting the oral absorption of the drug. Drug solubility and permeability are uniquely correlated because drug permeability is related to the membrane / water parti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K31/36A61K9/46A61P25/08A61K31/515A61K31/4166A61K31/513
CPCA61K31/36A61K9/146A61K9/2018A61K9/0095A61P25/08A61K9/0007A61K31/515A61K31/4166A61K31/513
Inventor 何伟王影
Owner CHINA PHARM UNIV
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