Quality by Design (QbD) Approach to Develop Colon-Specific Ketoprofen Hot-Melt Extruded Pellets: Impact of Eudragit S 100 Coating on the In Vitro Drug Release

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2024 Oct 26

PMID 39458597

Authors

Sateesh Kumar Vemula

Sagar Narala

Prateek Uttreja

Nagarjuna Narala

Bhaskar Daravath

Chamundeswara Srinivasa Akash Kalla

Srikanth Baisa

Siva Ram Munnangi

Naveen Chella

Michael A Repka

Affiliations

Soon will be listed here.

Abstract

Background: A pelletizer paired with hot-melt extrusion technology (HME) was used to develop colon-targeted pellets for ketoprofen (KTP). Thermal stability and side effects in the upper gastrointestinal tract made ketoprofen more suitable for this work.

Methods: The pellets were prepared using the enzyme-triggered polymer Pectin LM in the presence of HPMC HME 4M, followed by pH-dependent Eudragit S 100 coating to accommodate the maximum drug release in the colon by minimizing drug release in the upper gastrointestinal tract (GIT). Box-Behnken Design (BBD) was used for response surface optimization of the proportion of different independent variables like Pectin LM (A), HPMC HME 4M (B), and Eudragit S 100 (C) required to lower the early drug release in upper GIT and to extend the drug release in the colon.

Results: Solid-state characterization studies revealed that ketoprofen was present in a solid solution state in the hot-melt extruded polymer matrix. The desired responses of the prepared optimized KTP pellets obtained by considering the designed space showed 1.20% drug release in 2 h, 3.73% in the first 5 h of the lag period with the help of Eudragit S 100 coating, and 93.96% in extended release up to 24 h in the colonic region.

Conclusions: Hence, developing Eudragit-coated hot-melt extruded pellets could be a significant method for achieving the colon-specific release of ketoprofen.

Citing Articles

Self-Emulsifying Drug Delivery Systems (SEDDS): Transition from Liquid to Solid-A Comprehensive Review of Formulation, Characterization, Applications, and Future Trends.

Uttreja P, Karnik I, Youssef A, Narala N, Elkanayati R, Baisa S Pharmaceutics. 2025; 17(1).

PMID: 39861711 PMC: 11768142. DOI: 10.3390/pharmaceutics17010063.

References

Dumpa N, Sarabu S, Bandari S, Zhang F, Repka M . Chronotherapeutic Drug Delivery of Ketoprofen and Ibuprofen for Improved Treatment of Early Morning Stiffness in Arthritis Using Hot-Melt Extrusion Technology. AAPS PharmSciTech. 2018; 19(6):2700-2709. PMC: 6067978. DOI: 10.1208/s12249-018-1095-z. View

Lee S, Bajracharya R, Min J, Han J, Park B, Han H . Strategic Approaches for Colon Targeted Drug Delivery: An Overview of Recent Advancements. Pharmaceutics. 2020; 12(1). PMC: 7022598. DOI: 10.3390/pharmaceutics12010068. View

Vemula S, Bontha V . Colon targeted guar gum compression coated tablets of flurbiprofen: formulation, development, and pharmacokinetics. Biomed Res Int. 2013; 2013:287919. PMC: 3821905. DOI: 10.1155/2013/287919. View

Khotimchenko M . Pectin polymers for colon-targeted antitumor drug delivery. Int J Biol Macromol. 2020; . DOI: 10.1016/j.ijbiomac.2020.05.002. View

Wahlgren M, Axenstrand M, Hakansson A, Marefati A, Pedersen B . Methods to Study Colon Release: State of the Art and An Outlook on New Strategies for Better Biorelevant Release Media. Pharmaceutics. 2019; 11(2). PMC: 6410320. DOI: 10.3390/pharmaceutics11020095. View

Teruel A, Gonzalez-Alvarez I, Bermejo M, Merino V, Marcos M, Sancenon F . New Insights of Oral Colonic Drug Delivery Systems for Inflammatory Bowel Disease Therapy. Int J Mol Sci. 2020; 21(18). PMC: 7555849. DOI: 10.3390/ijms21186502. View

Tan D, Maniruzzaman M, Nokhodchi A . Development and Optimisation of Novel Polymeric Compositions for Sustained Release Theophylline Caplets (PrintCap) via FDM 3D Printing. Polymers (Basel). 2019; 12(1). PMC: 7023590. DOI: 10.3390/polym12010027. View

Narala S, Nyavanandi D, Mandati P, Youssef A, Alzahrani A, Kolimi P . Preparation and evaluation of hot-melt extruded pectin-based pellets containing ketoprofen for colon targeting. Int J Pharm X. 2023; 5:100156. PMC: 9830203. DOI: 10.1016/j.ijpx.2022.100156. View

Vemula S, Daravath B, Repka M . Quality by design (QbD) approach to develop fast-dissolving tablets using melt-dispersion paired with surface-adsorption method: formulation and pharmacokinetics of flurbiprofen melt-dispersion granules. Drug Deliv Transl Res. 2023; 13(12):3204-3222. DOI: 10.1007/s13346-023-01382-z. View

10.

Gu B, Linehan B, Tseng Y . Optimization of the Büchi B-90 spray drying process using central composite design for preparation of solid dispersions. Int J Pharm. 2015; 491(1-2):208-17. DOI: 10.1016/j.ijpharm.2015.06.006. View

11.

Varum F, Freire A, Fadda H, Bravo R, Basit A . A dual pH and microbiota-triggered coating (Phloral™) for fail-safe colonic drug release. Int J Pharm. 2020; 583:119379. DOI: 10.1016/j.ijpharm.2020.119379. View

12.

Vemula S, Daravath B, Gummadi S, Repka M . Formulation and Development of Flurbiprofen Colon-Specific Eudragit Coated Matrix Tablets: Use of a Novel Crude Banana Peel Powder as a Time-Dependent Polymer. AAPS PharmSciTech. 2023; 24(7):189. DOI: 10.1208/s12249-023-02646-0. View

13.

Vemula S . Formulation and pharmacokinetics of colon-specific double-compression coated mini-tablets: Chronopharmaceutical delivery of ketorolac tromethamine. Int J Pharm. 2015; 491(1-2):35-41. DOI: 10.1016/j.ijpharm.2015.06.007. View

14.

Shaqour B, Natsheh H, Kittana N, Jaradat N, Abualhasan M, Eid A . Modified Release 3D-Printed Capsules Containing a Ketoprofen Self-Nanoemulsifying System for Personalized Medical Application. ACS Biomater Sci Eng. 2024; 10(6):3833-3841. DOI: 10.1021/acsbiomaterials.4c00476. View

15.

Vemula S . A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets. AAPS PharmSciTech. 2015; 16(6):1465-73. PMC: 4666240. DOI: 10.1208/s12249-015-0340-y. View

16.

Elsayed E, Emam M . Application of Response Surface Methodology Using Face-centered Central Composite Design for Studying Long-Term Stability of Gliclazide-Loaded Multiparticulate Systems. J Pharm Sci. 2024; 113(8):2274-2285. DOI: 10.1016/j.xphs.2024.03.012. View

17.

Arevalo-Perez R, Maderuelo C, Lanao J . Recent advances in colon drug delivery systems. J Control Release. 2020; 327:703-724. DOI: 10.1016/j.jconrel.2020.09.026. View

18.

Nidhi , Rashid M, Kaur V, Hallan S, Sharma S, Mishra N . Microparticles as controlled drug delivery carrier for the treatment of ulcerative colitis: A brief review. Saudi Pharm J. 2016; 24(4):458-72. PMC: 4908146. DOI: 10.1016/j.jsps.2014.10.001. View

19.

Ibekwe V, Liu F, Fadda H, Khela M, Evans D, Parsons G . An investigation into the in vivo performance variability of pH responsive polymers for ileo-colonic drug delivery using gamma scintigraphy in humans. J Pharm Sci. 2006; 95(12):2760-6. DOI: 10.1002/jps.20742. View

20.

Guo Y, Zong S, Pu Y, Xu B, Zhang T, Wang B . Advances in Pharmaceutical Strategies Enhancing the Efficiencies of Oral Colon-Targeted Delivery Systems in Inflammatory Bowel Disease. Molecules. 2018; 23(7). PMC: 6099616. DOI: 10.3390/molecules23071622. View