Novel microwave-assisted solid dispersion technology enhances piroxicam dissolution and therapeutic efficacy: an in vitro and in vivo study

Charit Kumar; Arun Nanda

doi:10.69857/joapr.v13i1.921

Authors

Charit Kumar Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India https://orcid.org/0000-0002-8109-0591
Arun Nanda Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India

DOI:

https://doi.org/10.69857/joapr.v13i1.921

Keywords:

Piroxicam, Microwave-assisted drug formulation, In vivo anti-inflammatory activity, In vivo analgesic activity, PVP K30, Drug formulation technology

Abstract

Background: Piroxicam (PRX), a nonsteroidal anti-inflammatory drug, exhibits poor aqueous solubility, limiting its therapeutic efficacy. Enhancing solubility can directly improve bioavailability and therapeutic effectiveness. This study explores the development of a new solid dispersion (SD) system of PRX using polyvinylpyrrolidone (PVP K30) as a carrier by MW-assisted method. Methods: The involvement of microwave (MW) in the solvent evaporation method is a newer concept aimed at enhancing the solubility and in vivo bioavailability of PRX. Various ratios of PRX: PVPK30 (1:5, 1:7, 1:9, and 1:11 w/w) were evaluated using conventional and MW-assisted solvent evaporation methods and conducted in vitro dissolution studies. Results: The optimized MW-assisted formulation (1:7 w/w) exhibited 94.69±0.24% drug release in 15 minutes, showing a 5.37-fold increase compared to pure PRX (17.63%) and surpassing the marketed drug release (90.82±0.39%). Fourier Transform Infrared, Differential Scanning Calorimetry, Thermogravimetric analysis, Scanning Electron Microscopy, and powdered X-ray diffraction authenticated the OF. In vivo studies demonstrated significant enhancements (p<0.0001) compared to control. The anti-inflammatory activity showed increased paw oedema inhibition (44.4±0.4%) compared to control and pure PRX (35.37±0.3%). The analgesic activity of OF demonstrated improved pain response time (10.6±0.8 seconds) compared to control (4.2±0.5 seconds) and pure PRX (8.1±0.7 seconds). Conclusion: The SD developed via the MW-assisted drug formulation technique significantly enhances the solubility, bioavailability, and therapeutic efficacy of PRX, offering a potential strategy to improve clinical outcomes for similar drugs with solubility challenges.

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References

Bhalani DV, Nutan B, Kumar A, Singh Chandel AK. Bioavailability enhancement techniques for poorly aqueous soluble drugs and therapeutics. Biomedicines, 10, 2055 (2022) https://doi.org/10.3390/biomedicines10092055.

Tekade AR, Yadav JN. A review on solid dispersion and carriers used therein for solubility enhancement of poorly water soluble drugs. Adv. Pharm. Bull., 10, 359-369 (2020) https://doi.org/10.34172/apb.2020.044.

Schittny A, Huwyler J, Puchkov M. Mechanisms of increased bioavailability through amorphous solid dispersions: A review. Drug Deliv., 27, 110-127 (2020) https://doi.org/10.1080/10717544.2019.1704940.

Bhujbal SV, Mitra B, Jain U, Gong Y, Agrawal A, Karki S, et al. Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies. Acta Pharm. Sin. B., 11, 2505-2536 (2021) https://doi.org/10.1016/j.apsb.2021.05.014.

Pandi P, Bulusu R, Kommineni N, Khan W, Singh M. Amorphous solid dispersions: An update for preparation, characterization, mechanism on bioavailability, stability, regulatory considerations and marketed products. Int. J. Pharm., 586, 119560 (2020) https://doi.org/10.1016/j.ijpharm.2020.119560.

Qiang W, Löbmann K, McCoy CP, Andrews GP, Zhao M. Microwave-induced in situ amorphization: A new strategy for tackling the stability issue of amorphous solid dispersions. Pharmaceutics, 12, 655 (2020) https://doi.org/10.1016/j.ejps.2021.105858.

Virlley S, Shukla S, Arora S, Shukla D, Nagdiya D, Bajaj T, et al. Recent advances in microwave-assisted nanocarrier based drug delivery system: Trends and technologies. J. Drug Deliv. Sci. Tech., 87, 104842 (2023) https://doi.org/10.1016/j.jddst.2023.104842.

Zhang J, Thakkar R, Zhang Y, Maniruzzaman M. Microwave induced dielectric heating for the on-demand development of indomethacin amorphous solid dispersion tablets. J. Drug Deliv. Sci. Tech., 61, 102109 (2021) https://doi.org/10.1016/j.jddst.2020.102109.

Madan JR, Pawar AR, Patil RB, Awasthi R, Dua K. Preparation, characterization and in vitro evaluation of tablets containing microwave-assisted solid dispersions of apremilast. Polim. Med., (2018) https://doi.org/10.17219/pim/99801.

Caet MP, Monsores MA, Machado AK, Barth T, Sangoi MS, Todeschini V. Pharmacopoeial HPLC methodology improvement: A case study of piroxicam. Drug Analytical Research, 4, 50-57 (2020) https://doi.org/10.22456/2527-2616.108512.

Kasimbedu S, Chella S, Bharathi T, Pommala N, Mannepalli DSR. A Piroxicam Inclusion Complexation for Solubility Enhancement: Design and Development. J. Young Pharm., 14, 192 (2022) https://doi.org/10.5530/jyp.2022.14.36

Hempel N-J, Knopp MM, Berthelsen R, Zeitler JA, Löbmann K. The influence of drug and polymer particle size on the in situ amorphization using microwave irradiation. Eur. J. Pharm. Biopharm., 149, 77-84 (2020) https://doi.org/10.1016/j.ejpb.2020.01.019.

dos Santos KM, de Melo Barbosa R, Meirelles L, Vargas FGA, da Silva Lins AC, Camara CA, et al. Solid dispersion of β-lapachone in PVP K30 and PEG 6000 by spray drying technique. J. Therm. Anal. Calorim., 1-10 (2021) https://doi.org/10.1007/s10973-020-10473-9.

Zhang F, Mao J, Tian G, Jiang H, Jin Q. Preparation and characterization of furosemide solid dispersion with enhanced solubility and bioavailability. AAPS PharmSciTech, 23, 65 (2022) https://doi.org/10.1208/s12249-022-02208-w.

Rusdin A, Mohd Gazzali A, Ain Thomas N, Megantara S, Aulifa DL, Budiman A, et al. Advancing drug delivery paradigms: Polyvinyl pyrolidone (PVP)-based amorphous solid dispersion for enhanced physicochemical properties and therapeutic efficacy. Polymers, 16, 286 (2024) https://doi.org/10.3390/polym16020286.

Qiang W, Löbmann K, Knopp MM, McCoy CP, Andrews GP, Zhao M. Investigation into the role of the polymer in enhancing microwave-induced in situ amorphization. Int. J. Pharm., 609, 1-8 (2021) https://doi.org/10.1016/j.ijpharm.2021.121157.

Kaur K, Kaur T, Singh AP, Singh AP. Solid Dispersion Preparation by Different Methods to Improve Solubility & Dissolution Simvastatin. Int. j. pharm. drug. anal., 9, 241-253 (2021) https://doi.org/10.47957/ijpda.v9i4.491.

Hempel N-J, Knopp MM, Zeitler JA, Berthelsen R, Löbmann K. Microwave-induced in situ drug amorphization using a mixture of polyethylene glycol and polyvinylpyrrolidone. J. Pharm. Sci., 110, 3221-3229 (2021) https://doi.org/10.1016/j.xphs.2021.05.010.

Schver GC, Lee PI. On the usefulness of sink index in characterizing the degree of nonsinkness in dissolution studies. Int. J. Pharm., 605, 120845 (2021) https://doi.org/10.1016/j.ijpharm.2021.120845.

Yu D, Li J, Wang H, Pan H, Li T, Bu T, et al. Role of polymers in the physical and chemical stability of amorphous solid dispersion: A case study of carbamazepine. Eur. J. Pharm. Sci, 169, 106086 (2022) https://doi.org/10.1016/j.ejps.2021.106086.

Bajwa N, Singh M, Naryal S, Mahal S, Mehta S, Madan J, et al. Formulation Development and Assessment of Solid Dispersion and Hydrotropy for BCS Class II Drug Solubility Enhancement. Lett. Drug Des. Discov., 21, 305-319 (2024) https://doi.org/10.2174/1570180819666220822115049.

Mohana M, Vijayalakshmi S. Development and characterization of solid dispersion-based orodispersible tablets of cilnidipine. Beni-Suef Univ. J. Basic Appl. Sci., 11, 1-12 (2022) https://doi.org/10.1186/s43088-022-00259-3.

Yu JY, Kim JA, Joung HJ, Ko JA, Park HJ. Preparation and characterization of curcumin solid dispersion using HPMC. J. Food Sci., 85, 3866-3873 (2020) https://doi.org/10.1111/1750-3841.15489.

Saboo S, Moseson DE, Kestur US, Taylor LS. Patterns of drug release as a function of drug loading from amorphous solid dispersions: A comparison of five different polymers. Eur. J. Pharm. Sci., 155, 105514 (2020) https://doi.org/10.1016/j.ejps.2020.105514.

Vasconcelos T, Prezotti F, Araújo F, Lopes C, Loureiro A, Marques S, et al. Third-generation solid dispersion combining Soluplus and poloxamer 407 enhances the oral bioavailability of resveratrol. Int. J. Pharm., 595, 120245 (2021) https://doi.org/10.1016/j.ijpharm.2021.120245.

Alshehri S, Imam SS, Altamimi MA, Hussain A, Shakeel F, Elzayat E, et al. Enhanced dissolution of luteolin by solid dispersion prepared by different methods: physicochemical characterization and antioxidant activity. ACS omega, 5, 6461-6471 (2020) https://doi.org/10.1021/acsomega.9b04075.

Nupur MA, Rahman MM, Akter K, Hanif KB, Sharna JF, Sarker MS, et al. Preparation and characterization of naproxen solid dispersion using different hydrophilic carriers and in-vivo evaluation of its analgesic activity in mice. Heliyon, 9, (2023) https://doi.org/10.1016/j.heliyon.2023.e15432.

Hermans A, Milsmann J, Li H, Jede C, Moir A, Hens B, et al. Challenges and strategies for solubility measurements and dissolution method development for amorphous solid dispersion formulations. The AAPS Journal, 25, 11 (2022) https://doi.org/10.1208/s12248-022-00760-8.

Browne E, Worku ZA, Healy AM. Physicochemical properties of poly-vinyl polymers and their influence on ketoprofen amorphous solid dispersion performance: A polymer selection case study. Pharmaceutics, 12, 433 (2020) https://doi.org/10.3390/pharmaceutics12050433.

Kurakula M, Rao GK. Pharmaceutical assessment of polyvinylpyrrolidone (PVP): As excipient from conventional to controlled delivery systems with a spotlight on COVID-19 inhibition. J. Drug Deliv. Sci. Tech., 60, 102046 (2020) https://doi.org/10.1016/j.jddst.2020.102046.

Pironi AM, Eloy JdO, Rodero CF, Antonio SG, Alonso JD, Chorilli M. PVP solid dispersions containing Poloxamer 407 or TPGS for the improvement of ursolic acid release. Braz. J. Pharm. Sci., 59, 1-19 (2023) https://doi.org/10.1590/s2175-97902023e21217.

Chavan RB, Lodagekar A, Yadav B, Shastri NR. Amorphous solid dispersion of nisoldipine by solvent evaporation technique: preparation, characterization, in vitro, in vivo evaluation, and scale up feasibility study. Drug Deliv. Transl. Res., 10, 903-918 (2020) https://doi.org/10.1007/s13346-020-00775-8.

Tantishaiyakul V, Kaewnopparat N, Ingkatawornwong S. Properties of solid dispersions of piroxicam in polyvinylpyrrolidone K-30. Int. J. Pharm., 143, 59-66 (1996) https://doi.org/10.1016/S0378-5173(96)04687-X.

Sohn JS, Kim EJ, Park J-W, Choi J-S. Piroxicam ternary solid dispersion system for improvement of dissolution (%) and in vitro anti-inflammation effects. Mater. Sci. Eng. B., 261, 114651 (2020) https://doi.org/10.1016/j.mseb.2020.114651.