Process Optimization for the Continuous Production of a Gastroretentive Dosage Form Based on Melt Foaming

Overview

Journal AAPS PharmSciTech

Publisher Springer

Specialty Pharmacology

Date 2021 Jun 22

PMID 34155595

Citations 5

Authors

Adam Haimhoffer

Gabor Vasvari

Gyorgy Trencsenyi

Monika Beresova

Istvan Budai

Zsuzsa Czomba

Agnes Rusznyak

Judit Varadi

Ildiko Bacskay

Zoltan Ujhelyi

Palma Feher

Miklos Vecsernyes

Ferenc Fenyvesi

Affiliations

Soon will be listed here.

Abstract

Several drugs have poor oral bioavailability due to low or incomplete absorption which is affected by various effects as pH, motility of GI, and enzyme activity. The gastroretentive drug delivery systems are able to deal with these problems by prolonging the gastric residence time, while increasing the therapeutic efficacy of drugs. Previously, we developed a novel technology to foam hot and molten dispersions on atmospheric pressure by a batch-type in-house apparatus. Our aim was to upgrade this technology by a new continuous lab-scale apparatus and confirm that our formulations are gastroretentive. At first, we designed and built the apparatus and continuous production was optimized using a Box-Behnken experimental design. Then, we formulated barium sulfate-loaded samples with the optimal production parameters, which was suitable for in vivo imaging analysis. In vitro study proved the low density, namely 507 mg/cm, and the microCT record showed high porosity with 40 μm average size of bubbles in the molten suspension. The BaSO-loaded samples showed hard structure at room temperature and during the wetting test, the complete wetting was detected after 120 min. During the in vivo study, the X-ray taken showed the retention of the formulation in the rat stomach after 2 h. We can conclude that with our device low-density floating formulations were prepared with prolonged gastric residence time. This study provides a promising platform for marketed active ingredients with low bioavailability.

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References

Drenckhan W, Saint-Jalmes A . The science of foaming. Adv Colloid Interface Sci. 2015; 222:228-59. DOI: 10.1016/j.cis.2015.04.001. View

Rajput P, Singh D, Pathak K . Bifunctional capsular dosage form: novel fanicular cylindrical gastroretentive system of clarithromycin and immediate release granules of ranitidine HCl for simultaneous delivery. Int J Pharm. 2013; 461(1-2):310-21. DOI: 10.1016/j.ijpharm.2013.11.053. View

Iglesias N, Galbis E, Romero-Azogil L, Benito E, Lucas R, Garcia-Martin M . In-Depth Study into Polymeric Materials in Low-Density Gastroretentive Formulations. Pharmaceutics. 2020; 12(7). PMC: 7408198. DOI: 10.3390/pharmaceutics12070636. View

Lopes C, Bettencourt C, Rossi A, Buttini F, Barata P . Overview on gastroretentive drug delivery systems for improving drug bioavailability. Int J Pharm. 2016; 510(1):144-58. DOI: 10.1016/j.ijpharm.2016.05.016. View

Simons F, Wagner K . Modeling, design and manufacture of innovative floating gastroretentive drug delivery systems based on hot-melt extruded tubes. Eur J Pharm Biopharm. 2019; 137:196-208. DOI: 10.1016/j.ejpb.2019.02.022. View

Fukuda M, Peppas N, McGinity J . Floating hot-melt extruded tablets for gastroretentive controlled drug release system. J Control Release. 2006; 115(2):121-9. DOI: 10.1016/j.jconrel.2006.07.018. View

Tripathi J, Thapa P, Maharjan R, Jeong S . Current State and Future Perspectives on Gastroretentive Drug Delivery Systems. Pharmaceutics. 2019; 11(4). PMC: 6523542. DOI: 10.3390/pharmaceutics11040193. View

Vasvari G, Haimhoffer A, Horvath L, Budai I, Trencsenyi G, Beresova M . Development and Characterisation of Gastroretentive Solid Dosage Form Based on Melt Foaming. AAPS PharmSciTech. 2019; 20(7):290. PMC: 6700043. DOI: 10.1208/s12249-019-1500-2. View

Shin S, Kim T, Jeong S, Chung S, Lee D, Kim D . Development of a gastroretentive delivery system for acyclovir by 3D printing technology and its in vivo pharmacokinetic evaluation in Beagle dogs. PLoS One. 2019; 14(5):e0216875. PMC: 6519832. DOI: 10.1371/journal.pone.0216875. View

10.

Wu Y, Zhang W, Huang J, Luo Z, Li J, Wang L . Mucoadhesive improvement of alginate microspheres as potential gastroretentive delivery carrier by blending with Bletilla striata polysaccharide. Int J Biol Macromol. 2019; 156:1191-1201. DOI: 10.1016/j.ijbiomac.2019.11.156. View

11.

Ismail R, Sovany T, Gacsi A, Ambrus R, Katona G, Imre N . Synthesis and Statistical Optimization of Poly (Lactic-Co-Glycolic Acid) Nanoparticles Encapsulating GLP1 Analog Designed for Oral Delivery. Pharm Res. 2019; 36(7):99. PMC: 6513835. DOI: 10.1007/s11095-019-2620-9. View

12.

Streubel A, Siepmann J, Bodmeier R . Drug delivery to the upper small intestine window using gastroretentive technologies. Curr Opin Pharmacol. 2006; 6(5):501-8. DOI: 10.1016/j.coph.2006.04.007. View

13.

Hao S, Wang B, Wang Y . Density-dependent gastroretentive microparticles motion in human gastric emptying studied using computer simulation. Eur J Pharm Sci. 2015; 70:72-81. DOI: 10.1016/j.ejps.2015.01.009. View

14.

Vedha H, Brahma R, Samyuktha R . Floating drug delivery of nevirapine as a gastroretentive system. J Young Pharm. 2011; 2(4):350-5. PMC: 3019371. DOI: 10.4103/0975-1483.71622. View

15.

Dios P, Szigeti K, Budan F, Pocsik M, Veres D, Mathe D . Influence of barium sulfate X-ray imaging contrast material on properties of floating drug delivery tablets. Eur J Pharm Sci. 2016; 95:46-53. DOI: 10.1016/j.ejps.2016.09.034. View

16.

Schneider F, Koziolek M, Weitschies W . In Vitro and In Vivo Test Methods for the Evaluation of Gastroretentive Dosage Forms. Pharmaceutics. 2019; 11(8). PMC: 6723944. DOI: 10.3390/pharmaceutics11080416. View

17.

Oh T, Kim J, Ha J, Chi S, Rhee Y, Park C . Preparation of highly porous gastroretentive metformin tablets using a sublimation method. Eur J Pharm Biopharm. 2012; 83(3):460-7. DOI: 10.1016/j.ejpb.2012.11.009. View

18.

Dios P, Nagy S, Pal S, Pernecker T, Kocsis B, Budan F . Preformulation studies and optimization of sodium alginate based floating drug delivery system for eradication of Helicobacter pylori. Eur J Pharm Biopharm. 2015; 96:196-206. DOI: 10.1016/j.ejpb.2015.07.020. View

19.

Klausner E, Lavy E, Friedman M, Hoffman A . Expandable gastroretentive dosage forms. J Control Release. 2003; 90(2):143-62. DOI: 10.1016/s0168-3659(03)00203-7. View

20.

Chaves de Souza M, Sabio R, Ribeiro T, Dos Santos A, Meneguin A, Chorilli M . Highlighting the impact of chitosan on the development of gastroretentive drug delivery systems. Int J Biol Macromol. 2020; 159:804-822. PMC: 7232078. DOI: 10.1016/j.ijbiomac.2020.05.104. View