Formulation development and evaluation of in situ nasal gel of poorly water soluble drug using mixed solvency concept

Archana Agrawal, Maheshwari RK

Abstract


The present study was aimed to develop a mucoadhesive in situ nasal gel containing domperidone with enhanced drug loading and transnasal permeation properties, which were achieved by improving drug solubility using the concept of
mixed solvency. Poloxamer 407 was used as thermosensitive polymer and carbopol 934P as mucoadhesive polymer. Initially solubility of domperidone was enhanced in aqueous solution by using various solubilizers like sodium citrate (SC), urea (UR), polyvinyl pyrrolidone (PVP), polyethylene glycol (PEG), propylene glycol (PG) etc, individually and as a combination of two, three, and four solvents, respectively. Maximum solubility of domperidone was achieved at 30% w/w solvent concentration, containing mixed blend of PVP K30 (7.5% w/w) + PEG 400 (7.5% w/w) + PEG 600 (7.5% w/w) + Propylene Glycol
(7.5% w/w), enhancing solubility of domperidone by 172.20 times as compared to its solubility in water. In situ gel was prepared by cold technique. Evaluation of the prepared gel was carried out, including properties like phase transition
temperature, viscosity, in vitro drug release, drug content, transnasal permeation and stability studies. In vitro drug release studies of aqueous solution of mixed blend were performed and permeability coefficient was found to be 1.576 × 10-02
cm/hr and flux was found to be 8.64 μg/cm2hr. Similarly in vitro studies for in situ nasal gel were performed and percent cumulative drug release was 73.05±0.57% in 6 h.Transnasal drug permeation studies results in flux value of 7.04 μg/cm2hr and percent cumulative drug permeated across the membrane as 86.62±0.992%.The results from stability studies revealed that the prepared thermogel showed no significant decrease in drug content and no physicochemical change was observed upon storage in different temperature conditions resulting as a stable formulation.


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References


Illum L. Transport of drugs from the nasal cavity to the central nervous

system. Eur J Pharm Sci 2000;11:1-18.

Talegaonkar S, Mishra PR. Intranasal delivery: An approach to bypass

the blood brain barrier. Indian J Pharmacol 2004;36:140-147.

Sian LT, Lim F, Brown MB, Martin GP. Phisiological factors affecting nasal

drug delivery. In: Tauitou Elka, Barry Brian W, editors. Enhancement in

Drug Delivery. United Kingdom: CRC Press; 2006. p. 355-72.

Zia H, Dondeti P, Needham TE. Bioadhesive and formulation parameters

affecting nasal absorption. Int J Pharm 1995;127:115-33.

Bhise SB, Yadav AV, Avachat AM, Malayandi R. Bioavailability of

intranasal drug delivery system. Asian J Pharm 2008;2:201-15.

Maheshwari RK, Rajagopalan R. Solubilization of ibuprofen by mixed

solvency approach. Indian Pharm 2009;8:81-4.

Maheshwari RK. "Mixed solvency approach" boon for solubilization of

poorly water soluble drugs. Asian J Pharm 2010;1:60-3.

Maheshwari RK. Mixed solvency- A novel concept for solubilization of

poorly water souble drugs. J Tech Eng Sci 2009;1:39-43.

Shah S, Agrawal M, Agrawal A. Solubilization of furosemide by mixed

solvency approch. J Pharm Res 2010;3:2732-3.

Zaki NM, Awad GA, Mortada ND, Abd Elhady SS. Enhanced bioavalibility 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.

Pisal SS, Padarkar AR, Mahadik KR, Kadam SS. Pluronic gels for nasal

delivery of Vitamin B12. Part I: preformulation study. Int J Pharm

;270:37-45.

Pisal SS, Reddy P, Padarkar AR, Mahadik KR, Kadam SS. Nasal melatonin gels using pluronic PF-127 for chronobiological treatment of sleep disorder. Indian J Biotech 2004;3:369-77.

Majithiya RJ, Ghosh PK, Umrethia ML, Murthy RS. Thermoreversible-

mucoadhesive gel for nasal delivery of sumatriptan. AAPS Pharmscitech

;7:67.

Maheshwari RK, Indurkhya A. Formulation and evaluation of aceclofenac injection made by mixed hydrotropic solubilization technique. Iran J Pharm Sci 2010;9:233-42.

Mahajan HS, Gattani SG. Gellan gum based microparticles of

metoclopromide hydrochloride for intranasal delivery: development

and evaluation. Chem Pharm Bull (Tokyo) 2009;57:388-392.

Pisal S, Shelke V, Mahadik K, Kadam S. Effect of organogel components on in vitro nasal delivery of propranolol hydrochloride. AAPS

Pharmscitech 2004;5:e63.

Maheshwari RK. Solid dispersion and syrup formulation of poorly water

soluble drugs by hydrotropy. Indian Pharm 2006;70:22-30.




DOI: http://dx.doi.org/10.22377/ajp.v5i3.98

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