Streamlining the development of an industrial dry granulation process for an immediate release tablet with systems modelling

This study aimed to develop a novel sustained release pellet of loxoprofen sodium (LXP) by coating a dissolution-rate controlling sub-layer containing hydroxypropyl methyl cellulose (HPMC) and citric acid, and a second diffusion-rate controlling layer containing aqueous dispersion of ethyl cellulose (ADEC) on the surface of a LXP conventional pellet, and to compare its performance in vivo with an immediate release tablet (Loxinon®). A three-level, three-factor Box-Behnken design and the response surface model (RSM) were used to investigate and optimize the effects of the citric acid content in the sub-layer, the sub-layer coating level, and the outer ADEC coating level on the in vitro release profiles of LXP sustained release pellets. The pharmacokinetic studies of the optimal sustained release pellets were performed in fasted beagle dogs using an immediate release tablet as a reference. The results illustrated that both the citric acid (CA) and ADEC as the dissolution- and diffusion-rate controlling materials significantly decreased the drug release rate. The optimal formulation showed a pH-independent drug release in media at pH above 4.5 and a slightly slow release in acid medium. The pharmacokinetic studies revealed that a more stable and prolonged plasma drug concentration profile of the optimal pellets was achieved, with a relative bioavaibility of 87.16% compared with the conventional tablets. This article provided a novel concept of two-step control of the release rate of LXP, which showed a sustained release both in vitro and in vivo.

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Converting a batch based high-shear granulation process to a continuous dry granulation process; a demonstration with ketoprofen tablets

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2020.105381 ◽

2020 ◽

Vol 151 ◽

pp. 105381

Author(s):

Krista Taipale-Kovalainen ◽

Jarkko Ketolainen ◽

Ossi Korhonen ◽

Tuomas Ervasti

Keyword(s):

High Shear ◽

Granulation Process ◽

Dry Granulation

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IMMEDIATE RELEASE TABLET OF ANTIHYPERTENSIVE DRUG OLMESARTAN MEDOXOMILE

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v3i2.427 ◽

2013 ◽

Vol 3 (2) ◽

Cited By ~ 1

Author(s):

Mayur V Mahida ◽

M M Gupta

Keyword(s):

Antihypertensive Drug ◽

Immediate Release ◽

Release Tablet

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Optimized chronomodulated dual release bilayer tablets of fexofenadine and montelukast: quality by design, development, and in vitro evaluation

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-019-0006-9 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 1

Author(s):

Bhupendra Singh ◽

Geetanjali Saini ◽

Manish Vyas ◽

Surajpal Verma ◽

Sourav Thakur

Keyword(s):

Drug Release ◽

Sustained Release ◽

Quality By Design ◽

Immediate Release ◽

Oral Dosage ◽

Nocturnal Asthma ◽

Sustained Release Tablet ◽

Bilayer Tablets ◽

Dual Release ◽

Release Tablet

Abstract Background The conventional oral dosage forms are not effective in dealing with chronopathological conditions, such as nocturnal asthma. Therefore, there is an unmet need to develop a delivery system that can deliver drug as per the chronopharmacology of the diseases. The purpose of the study is to use quality by design (QbD) technique and pulsatile principles for the development of Eudragit-coated dual release bilayer tablets. The dual layer consists of immediate release layer of fexofenadine HCl and sustained release layer of montelukast sodium. Results The quality target product profile of the formulation was developed, and the critical quality attributes were identified. Three-level, three-factor Box-Behnken design was used for the optimization of the bilayer tablets. Based on the design, a total of 13 formulation combinations (F1–F13 and M1–M13) were made having acceptable micromeritic properties. The developed immediate and sustained release layers were evaluated for physicochemical properties. Depending upon the value of the diffusion exponent, the Fickian diffusion mechanism is dominant among immediate and sustained release tablet layers. Response curve for immediate release layer showed that concentrations of sodium starch glycolate and sodium bicarbonate had a negative effect on disintegration time and a positive effect on drug release. For sustained release tablet layer, concentrations of HPMC E 5 LV and magnesium stearate had a significant effect on drug release. The ANOVA and diagnostic plots confirmed the significance and goodness of fit of the used model. Based on desirability plot values, optimized formulation was developed and coated with Eudragit coat. The coated bilayer tablet showed met the requirement of providing an immediate release during the first hour and a sustained release action for a period of more than 8 h after passing the gastric region. Conclusions The formulation can be fruitful in curbing the menace of nocturnal asthma and providing a high degree of patient compliance as the patient will not have to wake up at night to take the medication.

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