DEVELOPMENT OF METOCLOPRAMIDE HYDROCHLORIDE IN SITU GEL: NASAL DELIVERY AND PHARMACOKINETICS IN NEW ZEALAND RABBITS

UPENDRA C GALGATTE; PRAVIN D CHAUDHARI

doi:10.22159/ajpcr.2019.v12i4.31779

Authors

UPENDRA C GALGATTE Department of Pharmaceutics, Modern College of Pharmacy, Pune, Maharashtra, India.
PRAVIN D CHAUDHARI Department of Pharmaceutics, Modern College of Pharmacy, Pune, Maharashtra, India.

DOI:

https://doi.org/10.22159/ajpcr.2019.v12i4.31779

Keywords:

antiemetic, mucoadhesive, nasal, poloxamer 407, thermoreversible

Abstract

Objective: Systemic bioavailability of metoclopramide hydrochloride (MCH) is 32–80% by oral route. The study was targeted to develop in situ gel of MCH for nasal delivery and to study its pharmacokinetics in healthy rabbits. Pre-systemic metabolism can be overcome.

Methods: Poloxamer 407 (P407) aqueous solutions were prepared by cold method. In 32 factorial design, independent variables were Carbopol 934P and polyethylene glycol 6000 (PEG 6000), and dependent responses were gelation temperature, mucoadhesive strength, and drug release. A Pharmacokinetic study was carried out in New Zealand rabbits. The optimized in situ gel (1 mg/ml) was compared with marketed Reglan® (2 mg/2 ml) injection. Area under the curve (AUC), Cmax, and Tmax were estimated.

Results: F2 was an optimized formulation. The study showed that P407 solutions formed a gel at nasal temperature 34°C having mucoadhesive strength 806.12±3.45 dyne/cm2. MCH release was found to be 93.74±1.31% within 6 h. Histopathological examination of formulation F2 exhibited safety to the nasal mucosa. The pH of formulations was 5.1±0.1 to 5.6±0.1 in the range of pH of nasal cavity. Plasma samples were analyzed by liquid chromatography/mass spectroscopy (LC/MS). The area under curve AUC0-4 for in situ gel by nasal route was 2716±4.617 ng/h/ml and for marketed solution by intravenous route was 2874±1.0816 ng/h/ml. These were comparable. Nasal bioavailability was found 94.50% from in situ gel. Duration of action was longer, and steady-state concentration was found for in situ gel.

Conclusion: In situ gel was capable to release MCH in systemic circulation. In vivo study in rabbits has proved the improved bioavailability of MCH administered nasally. The optimized gel preparation was found to be promising for improved bioavailability.

Downloads

Download data is not yet available.

References

Mahajan HS, Gattani S. In situ gels of metoclopramide hydrochloride for intranasal delivery: In vitro evaluation and in vivo pharmacokinetic study in rabbits. Drug Deliv 2010;17:19-27.

Jadhav KR, Gambhire MN, Shaikh IM, Kadam VJ, Pisal SS. Nasal drug delivery system-factors affecting and applications. Curr Drug Ther 2007;2:27-38.

Thorat YS, Sarvagod AM, Kulkarni SV, Hosmani AH. Treatment of mouth ulcer by curcumin loaded thermoreversible mucoadhesive gel: A technical note. Int J Pharm Pharm Sci 2015;7:399-402.

Ruel-Gariépy E, Leroux JC. In situ-forming hydrogels review of temperature-sensitive systems. Eur J Pharm Biopharm 2004;58:409-26.

Majithiya RJ, Ghosh PK, Umrethia ML, Murthy RS. Thermoreversible-mucoadhesive gel for nasal delivery of sumatriptan. AAPS PharmSciTech 2006;7:67.

Pagar SA, Shinkar DM, Saudagar RB. Development and evaluation of in situ nasal mucoadhesive gel of metoprolol succinate by using 32 factorial design. Int J Pharm Pharm Sci 2014;6:218-23.

Kavita K, Rajas NJ. Sustained ophthalmic delivery of levofloxacin hemihydrate from an ion activated in situ gelling system. Int J Pharm Tech Res 2011;3:702-6.

Miller SC, Donovan MD. Effivity of poloxamer 407 gels on the miotic activity of pilocarapine nitrate in rabbits. Int J Pharm 1982;12:142-52.

Shaikh H, Gattani S, Nerkar P. In-situ gelling system based on thiolatedgellan gum as new carrier for nasal administration of dimenhydrinate. Int J Pharm Sci Nanotech 2009;2:544-50.

Choi HG, Oh YK, Kim CK. In situ gelling and mucoadhesive liquid suppository containing acetaminophen: Enhanced bioavailability. Int J Pharm 1998;165:23-32.

Sahu BP, Sharma HK. Nasal delivery of felodopine using hydrogel matrix. J Glob Trends Pharm Sci 2011;2:296-309.

Zaki NM, Awad GA, Mortada ND, Elhady SS. Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties. Eur J Pharm Sci 2007;32:296-307.

Noha MZ, Gehanne AA, Nahed DM, Seham S, Abd E. Enhance bioavailability of metoclopramide hydrochloride by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties. Eur J Pharm Sci 2007;32:296-307.

Kassab HJ, Thomas LM, Jabir SA. Development and physical characterization of a periodontal bioadhesive gel of gatifloxacin. Int J Appl Pharm 2017;9:31-6

Mygind N, Dahl R. Anatomy, physiology and function of the nasal cavity in health and disease. Adv Drug Del Rev 1998;29:3-13.

Kabanov AV, Batrakova EV, Alakhov VY. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release 2002;82:189-212.

Edsman K, Carlfors J, Petersson R. Rheological evaluation of poloxamer as an in situ gel for ophthalmic use. Eur J Pharm Sci 1998;6:105-12.

Efentakis M, Koutlis A, Vlachou M. Development and evaluation of oral multiple-unit and single-unit hydrophilic controlled-release systems. AAPS Pharm Sci Tech 2000;1:E34.

Jimenez-Kairuz AF, Allemandi DA, Manzo RH. Equilibrium properties and mechanism of kinetic release of metoclopramide from carbomer hydrogels. Int J Pharm 2003;250:129-36.

Desai SD, Blanchard J. In vitro evaluation of pluronic F127-based controlled-release ocular delivery systems for pilocarpine. J Pharm Sci 1998;87:226-30.

Peppas NA. Analysis of fickian and non-fickian drug release from polymers. Pharm Acta Helv 1985;60:110-1.

Duchateau JE, Zuidema J, Albers W, Merkus M. Nasal absorption of alprenolol and metoprolol. Int J Pharm 1996;34:131-6.