FORMULATION AND EVALUATION OF AZELNIDIPINE FAST-DISSOLVING TABLETS

BALA HEMALATHA; ANNE RAMU; SURYADEVARA VIDYADHARA

doi:10.22159/ijap.2025v17i1.52398

Authors

BALA HEMALATHA Acharya Nagarjuna University College of Pharmaceutical Sciences, Acharya Nagarjuna University, Guntur, Andhra Pradesh, India https://orcid.org/0009-0000-0765-7986
ANNE RAMU Department of Pharmaceutics, Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Chowdavaram, Guntur, Andhra Pradesh, India
SURYADEVARA VIDYADHARA Department of Pharmaceutics, Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Chowdavaram, Guntur, Andhra Pradesh, India

DOI:

https://doi.org/10.22159/ijap.2025v17i1.52398

Keywords:

Azelnidipine, PEG 6000, Microcrystalline cellulose-polyethylene glycol (MCC-PEG) conjugate, Crospovidone, Croscarmellose sodium, Sodium starch glycolate, Fast dissolving tablets

Abstract

Objective: The main aim of the present study was to improve the solubility and rate of dissolution of azelnidipine and thereby increase oral bioavailability. Azelnidipine is a calcium channel blocker that lowers blood pressure by relaxing blood vessels and relieving pressure on them. Azelnidipine is a Biopharmaceutics Classification System (BCS) class II drug with low bioavailability.

Methods: The present study involves the preparation and evaluation of solid dispersion of azelnidipine by physical mixing, fusion and solvent evaporation method using polyethylene glycol 6000 (PEG 6000) as a carrier. The prepared solid dispersions were evaluated for various parameters like angle of repose, carr’s index, particle size, drug content, Scanning Electron Microscopy (SEM) analysis, Differential Scanning Calorimetry (DSC), X-ray diffraction (XRD) and in vitro dissolution studies. As part of the project, Microcrystalline Cellulose-Polyethylene Glycol (MCC-PEG) Conjugate, a novel superdisintegrant, was developed.

Results: Solid dispersions prepared by fusion (AF 6) in a drug-to-polymer ratio of 1:3 released 99.40% of the drug more quickly than pure drug and other dispersions. The optimized solid dispersion (AF6) was used to prepare fast-dissolving tablets of azelnidipine. In comparison to commercially available and alternative tablet formulations, the study suggests that azelnidipine tablets (AT 13), made with 5% microcrystalline cellulose-polyethylene glycol conjugate as a super disintegrant, exhibited rapid drug release of 99.92% in 15 min. The drug was released in the following order: MCC-PEG Conjugate>Crospovidone>Croscarmellose sodium>Sodium starch glycolate in all tablet preparations containing super disintegrants.

Conclusion: It can be inferred that MCC-PEG conjugate is an efficient super disintegrant by comparing its results with those of available commercial super disintegrants and caused the drug azelnidipine to release rapidly from fast-dissolving tablets.

Downloads

Download data is not yet available.

References

Tran P, Pyo YC, Kim DH, Lee SE, Kim JK, Park JS. Overview of the manufacturing methods of solid dispersion technology for improving the solubility of poorly water-soluble drugs and application to anticancer drugs. Pharmaceutics. 2019 Mar 19;11(3):132-58. doi: 10.3390/pharmaceutics11030132, PMID 30893899.

Shamsuddin FM, Fazil M, Ansari SH, Ali J. Development and evaluation of solid dispersion of spironolactone using fusion method. Int J Pharm Investig. 2016 Jan-Mar;6(1):63-8. doi: 10.4103/2230-973X.176490, PMID 27014621.

Ram CV. Therapeutic usefulness of a novel calcium channel blocker azelnidipine in the treatment of hypertension: a narrative review. Cardiol Ther. 2022 Dec;11(4):473-89. doi: 10.1007/s40119-022-00276-4, PMID 35969319.

Sharma A, Jain CP. Preparation and characterization of solid dispersions of carvedilol with PVP K30. Res Pharm Sci. 2010 Jan;5(1):49-56. PMID 21589768.

Hussain E, Osman ZA, Abdelrahman Md. Formulation and evaluation of solid dispersion tablets of furosemide using polyvinyl pyrrolidone K-30. Int J Curr Pharm Res. 2021 Jan 10;13(2):43-50. doi: 10.22159/ijcpr.2021v13i2.41554.

Hardikar SR, Mulla SS. Optimization of formulation of solid dispersion of furosemide by factorial design. Int J Pharm Pharm Sci. 2019 Nov 20;12(4):43-8. doi: 10.22159/ijpps.2020v12i4.36428.

Kaushik R, Verma R, Budhwar V, Kaushik D. Investigation of solid dispersion approach for the improvement of pharmaceutical characteristics of telmisartan using a central composite design. Int J App Pharm. 2023;15(5):245-54. doi: 10.22159/ijap.2023v15i5.47968.

Payal DB, Kauslya A, Jitendra VS. Formulation of solid dispersions for enhancement of solubility and dissolution rate of simvastatin. Int J Pharm Pharm Sci. 2021 Feb 23;13(7):94-100. doi: 10.22159/ijpps.2021v13i7.41205.

Madhavi N, Sudhakar B, Sravani U. Development and evaluation of itraconazole solid dispersion gel cutaneous delivery. Int J App Pharm. 2023;15(6):334-41. doi: 10.22159/ijap.2023v15i6.48978.

Shivaji Y, Deeliprao D, Sandeep K, Dilip S. Formulation and evaluation of fast dissolving tablet of lurasidone hydrochloride by using solid dispersion technique. Eur J Biomed Pharm Sci. 2021;8(9):737-46.

Van Den Mooter G, Wuyts M, Blaton N, Busson R, Grobet P, Augustijns P. Physical stabilisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25. Eur J Pharm Sci. 2001;12(3):261-9. doi: 10.1016/s0928-0987(00)00173-1, PMID 11113645.

Mahaparale PR, Thorat VP. Studies on solid dispersions of leflunomide. Asian J Pharm Clin Res. 2020 Jun;13(6):187-90.

Van Den Mooter G, Augustijns P, Blaton N, Kinget R. Physicochemical characterization of solid dispersions of temazepam with polyethylene glycol 6000 and PVP K30. International Journal of Pharmaceutics. 1998;164(1-2):67-80. doi: 10.1016/S0378-5173(97)00401-8.

Abdul Fattah AM, Bhargava HN. Preparation and in vitro evaluation of solid dispersions of halofantrine. Int J Pharm. 2002;235(1-2):17-33. doi: 10.1016/s0378-5173(01)00941-3, PMID 11879736.

Kinani AA, Taghi HS. Formulation and characterization of orodispersible tablet of glimepiride. J Adv Pharm Technol Res. 2022;13(4):252-60. doi: 10.4103/japtr.japtr_375_22, PMID 36568054.

Elkhodairy KA, Hassan MA, Afifi SA. Formulation and optimization of orodispersible tablets of flutamide. Saudi Pharm J. 2014;22(1):53-61. doi: 10.1016/j.jsps.2013.01.009, PMID 24493974.

Nikam VK, Shete SK, Khapare JP. Most promising solid dispersion technique of oral dispersible tablet. Beni Suef Univ J Basic Appl Sci. 2020 Dec 9;9(1):1-16. doi: 10.1186/s43088-020-00086-4.

Elkhodairy KA, Hassan MA, Afifi SA. Formulation and optimization of orodispersible tablets of flutamide. Saudi Pharm J. 2014 Jan;22(1):53-61. doi: 10.1016/j.jsps.2013.01.009, PMID 24493974.

Bhalekar MR, Desale SS, Madgulkar AR. Synthesis of MCC-PEG conjugate and its evaluation as a superdisintegrant. AAPS Pharm Sci Tech. 2010 Sep;11(3):1171-8. doi: 10.1208/s12249-010-9476-y, PMID 20661675.

Patel DM, Patel SP, Patel CN. Formulation and evaluation of fast-dissolving tablet containing domperidone ternary solid dispersion. Int J Pharm Investig. 2014;4(4):174-82. doi: 10.4103/2230-973X.143116, PMID 25426438.

Eisa AM, El Megrab NA, El Nahas HM. Formulation and evaluation of fast-dissolving tablets of haloperidol solid dispersion. Saudi Pharm J. 2022 Nov;30(11):1589-602. doi: 10.1016/j.jsps.2022.09.002, PMID 36465849.

Fouad SA, Malaak FA, El Nabarawi MA, Abu Zeid K. Development of orally disintegrating tablets containing solid dispersion of a poorly soluble drug for enhanced dissolution: in vitro optimization/in vivo evaluation. Plos One. 2020 Dec 31;15(12):e0244646. doi: 10.1371/journal.pone.0244646, PMID 33382789.

Dehghani H, Taheri A, Homayouni A. Design optimization and evaluation of orally disintegrating tablet of meloxicam using its menthol-based solid dispersions. Curr Drug Deliv. 2017;14(5):709-17. doi: 10.2174/1567201813666160504100532, PMID 27142108.

Dash GS, Murthy PN, Chowdary KA. Selection and optimization of most efficient superdisintegrant for the formulation of dispersible tablets of tramadol hydrochloride. Int J Pharm Pharm Sci. 2022 Jul;14(7):21-6. doi: 10.22159/ijpps.2022v14i7.43638.

Boghra RJ, Kothawade PC, Belgamwar VS, Nerkar PP, Tekade AR, Surana SJ. Solubility dissolution rate and bioavailability enhancement of irbesartan by solid dispersion technique. Chem Pharm Bull (Tokyo). 2011;59(4):438-41. doi: 10.1248/cpb.59.438, PMID 21467670.

Biswal S, Sahoo J, Murthy PN, Giradkar RP, Avari JG. Enhancement of dissolution rate of gliclazide using solid dispersions with polyethylene glycol 6000. AAPS Pharm Sci Tech. 2008 Jun;9(2):563-70. doi: 10.1208/s12249-008-9079-z, PMID 18459056.

Shamsuddin M, Fazil M, Ansari SH, Ali J. Development and evaluation of solid dispersion of spironolactone using fusion method. Int J Pharm Investig. 2016 Jan-Mar;6(1):63-8. doi: 10.4103/2230-973X.176490, PMID 27014621.

Singh SK, Som S, Shankhwar U. Formulation and optimization of solid dispersion of clopidogrel with PEG 6000. J Appl Pharm Sci. 2011;1(08):217-26.