Development of Gastro-floating drug delivery system by 3D Printing: Impact of formulation and design on the release profile of Baclofen

Authors

  • Nuha Mohammed Abdulkhaleq Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq.
  • Mowafaq M. Ghareeb Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq.

DOI:

https://doi.org/10.22317/jcms.v8i6.1304

Keywords:

Baclofen, Printing, Three-Dimensional, Gastro-Floating device, Sustained-Release, Fused Deposition Modelling

Abstract

Objectives: Baclofen is a skeletal muscle relaxant with a short half-life and a narrow absorption window in the upper part of the gastrointestinal tract, and this study aims to formulate a sustained-release tablet of baclofen and 3D printing of gastro-floating device and study the effect of various polymers and device design on the release profile of baclofen.

Method: Firstly, four formulas were produced through the hot-melt extrusion and direct compression of the extrudate to produce 30 mg baclofen tablets, then four gastro-floating devices (A, B, C, and D) were designed with two air pockets to enable the floating of the device and have drug-releasing windows with total surface area 4, 10, 20, and 40 mm2 respectively, for drug release. 3D printing of the devices was done by an FDM printer and the tablets were inserted into each device and test it for drug release.

Results: Decreasing the surface area of the drug releasing windows revealed a significant reduction in the dissolution of baclofen irrespective of the type of polymers and useful for sustained release formulation but may be associated with lag time. Devices with one and two releasing windows (Device B and C respectively) sometimes revealed similar dissolution profiles and this related to the position of the window regarding the surface of the dissolution media. Device D with four windows and a 40 mm2 surface area was found to produce more reliable results. F3 which contains Eudragit RS-100 as the main polymer showed sustained release in device D where the complete dissolution of the drug occurred in 12 hours, and the gastro-floating device remained floating all the time and was assayed for drug content, FT-IR, and DSC study.

Conclusion: Hot-melt extrusion was successfully employed to produce sustained release tablets of baclofen. FDM 3D printers are considered a potential tool to produce gastro-floating devices with the required design and release profile.

References

Psimadas D, Georgoulias P, Valotassiou V, Loudos G. Molecular Nanomedicine Towards Cancer : Journal of pharmaceutical sciences. 2012;101(7):2271–80.

Jamróz W, Szafraniec J, Kurek M, Jachowicz R. 3D Printing in Pharmaceutical and Medical Applications – Recent Achievements and Challenges. Pharmaceutical Research. 2018;35(9).

Parhi R. A review of three-dimensional printing for pharmaceutical applications: Quality control, risk assessment and future perspectives. Journal of Drug Delivery Science and Technology. 2021;64(April):102571.

Tan DK, Maniruzzaman M, Nokhodchi A. Advanced pharmaceutical applications of hot-melt extrusion coupled with fused deposition modelling (FDM) 3D printing for personalised drug delivery. Pharmaceutics. 2018;10(4):203.

Kolakovic R, Viitala T, Ihalainen P, … Sandler N. Printing technologies in fabrication of drug delivery systems. Expert Opinion on Drug Delivery. 2013;10(12):1711–23.

Goyanes A, Robles Martinez P, Buanz A, Basit AW, Gaisford S. Effect of geometry on drug release from 3D printed tablets. International Journal of Pharmaceutics. 2015;494(2):657–63.

Maniruzzaman M, Boateng JS, Snowden MJ, Douroumis D. A Review of Hot-Melt Extrusion: Process Technology to Pharmaceutical Products. ISRN Pharmaceutics. 2012;2012:1–9.

Tiwari R, Agarwal SK, Murthy RSR, Tiwari S. Formulation and evaluation of sustained release extrudes prepared via novel hot melt extrusion technique. Journal of Pharmaceutical Innovation. 2014;9(3):246–58.

Qi S, Craig DQM. Hot melt extruded transdermal fi lms based on amorphous solid dispersions in Eudragit RS PO : The inclusion of hydrophilic additives to develop moisture-activated release systems. International Journal of Pharmaceutics. 2016;514(1):270–81.

Cossé A, König C, Lamprecht A, Wagner KG. Hot Melt Extrusion for Sustained Protein Release: Matrix Erosion and In Vitro Release of PLGA-Based Implants. AAPS PharmSciTech. 2017;18(1):15–26.

Li Y, Lu M, Wu C. PVP VA64 as a novel release-modifier for sustained-release mini-matrices prepared via hot melt extrusion. Drug Delivery and Translational Research. 2018;8(6):1670–8.

Vanza JD, Patel RB, Dave RR, Patel MR. Polyethylene oxide and its controlled release properties in hydrophilic matrix tablets for oral administration. Pharmaceutical Development and Technology. 2020;25(10):1169–87.

Vengeliene V, Takahashi TT, Dravolina OA, … Spanagel R. Efficacy and side effects of baclofen and the novel GABA B receptor positive allosteric modulator CMPPE in animal models for alcohol and cocaine addiction. Psychopharmacology. 2018;235(7):1955–65.

Jeong HM, Weon KY, Shin BS, Shin S. 3D-printed gastroretentive sustained release drug delivery system by applying design of experiment approach. Molecules. 2020;25(10).

Tripathi J, Thapa P, Maharjan R, Jeong SH. Current state and future perspectives on gastroretentive drug delivery systems. Pharmaceutics. 2019;11(4).

Shin S, Kim TH, Jeong SW, … Shin BS. 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):1–17.

M. Jaimini ACR and YST. Formulation and Evaluation of Famotidine Floating Tablets. Current Drug Delivery. 2007;4:51–5.

Charoenying T, Patrojanasophon P, Ngawhirunpat T, … Opanasopit P. Fabrication of floating capsule-in- 3D-printed devices as gastro-retentive delivery systems of amoxicillin. Journal of Drug Delivery Science and Technology. 2020;55:101393.

Fu J, Yin H, Yu X, … Sheng F. Combination of 3D printing technologies and compressed tablets for preparation of riboflavin floating tablet-in-device (TiD) systems. International Journal of Pharmaceutics. 2018;549(1–2):370–9.

Wuis EW, Dirks MJM, Vree TB, Van der Kleijn E. Pharmacokinetics of baclofen in spastic patients receiving multiple oral doses. Pharmaceutisch Weekblad Scientific Edition. 1990;12(2):71–4.

Ibrahim M, Naguib YW, Sarhan HA, Abdelkader H. Preformulation-Assisted Design and Characterization of Modified Release Gastroretentive Floating Extrudates Towards Improved Bioavailability and Minimized Side Effects of Baclofen. Journal of Pharmaceutical Sciences. 2021;110(3):1227–39.

Lu J, Obara S, Liu F, … Kikuchi S. Melt Extrusion for a High Melting Point Compound with Improved Solubility and Sustained Release. AAPS PharmSciTech. 2018;19(1):358–70.

Anjali Devi N, Hadi MA, Rajitha P, Sharma JVC, Srinivasa Rao A. Formulation and evaluation of floating controlled release tablets of Imatinib mesylate using hydrophilic matrix system. International Journal of Pharmacy and Pharmaceutical Sciences. 2013;5(1):271–7.

Ansari KA, Vavia PR, Trotta F, Cavalli R. Cyclodextrin-based nanosponges for delivery of resveratrol: In vitro characterisation, stability, cytotoxicity and permeation study. AAPS PharmSciTech. 2011;12(1):279–86.

Lamichhane S, Park JB, Sohn DH, Lee S. Customized novel design of 3D printed pregabalin tablets for intra-gastric floating and controlled release using fused deposition modeling. Pharmaceutics. 2019;11(11):1–14.

Abdelkader H, Abdalla OY, Salem H. Formulation of controlled-release baclofen matrix tablets II: Influence of some hydrophobic excipients on the release rate and in vitro evaluation. AAPS PharmSciTech. 2008;9(2):675–83.

Correa G, Montero AV. Development of sustained release tablets containing solid dispersions of baclofen. Journal of fundemental and applied science. 2013;5(2):220–39.

Pereira GG, Figueiredo S, Fernandes AI, Pinto JF. Polymer selection for hot-melt extrusion coupled to fused deposition modelling in pharmaceutics. Pharmaceutics. 2020;12(9):1–63.

Farooq M, Harris M, Rabia S, Yousuf I. Development of extended release loxoprofen sodium multiparticulates using different hydrophobic polymers. Polymer Bulletin. 2018;(0123456789).

Ali MAM, Sabati AM, Ali BA. Formulation and evaluation of baclofen mucoadhesive buccal films. Fabad Journal of Pharmaceutical Sciences. 2017;42(3):179–90.

Ibraheem FQ, Gawhri FJAL. Preparation and in- vitro evaluation of Baclofen as an oral microsponge tablets. Iraqi Journal of Pharmaceutical Sciences. 2019;28(1):75–90.

Dillen K, Vandervoort J, Mooter G Van Den, Ludwig A. Evaluation of ciprofloxacin-loaded Eudragit ® RS100 or RL100 / PLGA nanoparticles. International Journal of Pharmaceutics. 2006;314(1):72–82.

Partheniadis I, Karantzalis AE, Shah RR, Al-Zoubi N, Nikolakakis I. Influence of compression at elevated temperature on the compactibility of thermo-mechanically processed polymers. Chemical Engineering Research and Design. 2020;156:64–75.

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Published

2022-12-26

How to Cite

Abdulkhaleq, N. M. ., & Ghareeb, M. M. . (2022). Development of Gastro-floating drug delivery system by 3D Printing: Impact of formulation and design on the release profile of Baclofen. Journal of Contemporary Medical Sciences, 8(6), 413–419. https://doi.org/10.22317/jcms.v8i6.1304