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Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet.
PLoS One. 2015; 10(6):e0126874.Plos

Abstract

INTRODUCTION

Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.

METHODOLOGY

Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted.

RESULTS AND DISCUSSION

Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours.

CONCLUSION

In conclusion, in order to suggest a better drug delivery system with constant favorable release, resulting in optimized absorption and less side effects, formulated CP-HPMC-SA based imatinib mesylate floating sustained-release tablets can be a promising candidate for cancer chemotherapy.

Authors+Show Affiliations

Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran.Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.Department of Pharmacy, Medical Faculty, University of Malaya, Kuala Lumpur, Malaysia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26035710

Citation

Kadivar, Ali, et al. "Formulation and in Vitro, in Vivo Evaluation of Effervescent Floating Sustained-release Imatinib Mesylate Tablet." PloS One, vol. 10, no. 6, 2015, pp. e0126874.
Kadivar A, Kamalidehghan B, Javar HA, et al. Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet. PLoS One. 2015;10(6):e0126874.
Kadivar, A., Kamalidehghan, B., Javar, H. A., Davoudi, E. T., Zaharuddin, N. D., Sabeti, B., Chung, L. Y., & Noordin, M. I. (2015). Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet. PloS One, 10(6), e0126874. https://doi.org/10.1371/journal.pone.0126874
Kadivar A, et al. Formulation and in Vitro, in Vivo Evaluation of Effervescent Floating Sustained-release Imatinib Mesylate Tablet. PLoS One. 2015;10(6):e0126874. PubMed PMID: 26035710.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet. AU - Kadivar,Ali, AU - Kamalidehghan,Behnam, AU - Javar,Hamid Akbari, AU - Davoudi,Ehsan Taghizadeh, AU - Zaharuddin,Nurul Dhania, AU - Sabeti,Bahareh, AU - Chung,Lip Yong, AU - Noordin,Mohamed Ibrahim, Y1 - 2015/06/02/ PY - 2014/09/25/received PY - 2015/04/08/accepted PY - 2015/6/3/entrez PY - 2015/6/4/pubmed PY - 2016/4/26/medline SP - e0126874 EP - e0126874 JF - PloS one JO - PLoS One VL - 10 IS - 6 N2 - INTRODUCTION: Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets. METHODOLOGY: Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted. RESULTS AND DISCUSSION: Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours. CONCLUSION: In conclusion, in order to suggest a better drug delivery system with constant favorable release, resulting in optimized absorption and less side effects, formulated CP-HPMC-SA based imatinib mesylate floating sustained-release tablets can be a promising candidate for cancer chemotherapy. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/26035710/Formulation_and_in_vitro_in_vivo_evaluation_of_effervescent_floating_sustained_release_imatinib_mesylate_tablet_ L2 - https://dx.plos.org/10.1371/journal.pone.0126874 DB - PRIME DP - Unbound Medicine ER -