Contributions on Formulation and Preliminary Evaluation of Ocular Colloidal Systems of Chitosan and Poloxamer 407 With Bupivacaine Hydrochloride

Abstract

The aim of this paper was the formulation and preliminary evaluation of colloidal systems with improved mechanical and mucoadhesive properties in order to increase ocular retention time and drug bioavailability. Polymeric mixtures of chitosan (0.3%), a pH-sensitive polymer, and poloxamer 407 (12%, 15%, 18%), thermoresponsive polymer, with bupivacaine hydrochloride (0.25%) were prepared. Gelling temperature, wettability, rheological behaviour and in vitro drug release were evaluated. The formulation containing 15% poloxamer 407 is converted to a colloidal dispersion at 35°C, the temperature of the ocular surface. Contact angle values of colloidal systems at physiological temperature (35°C) were lower than those corresponding to formulations at non-physiological temperature (25°C), indicating a higher spreadability over the ocular surface. Rheological studies have shown pseudoplastic behaviour and the poloxamer concentration increased the viscosity of the formulations. In vitro bupivacaine hydrochloride delivery from colloidal systems revealed that drug release mechanism followed Higuchi model. The colloidal dispersions with chitosan and poloxamer 407 could be viable alternatives to increase the bioavailability of bupivacaine hydrochloride in topical ocular anaesthesia. Rezumat Obiectivele acestei lucrări sunt formularea şi evaluarea preliminară a unor sisteme coloidale cu proprietăţi mecanice şi mucoadezive sporite care să asigure un timp de remanenţă crescut la nivel ocular şi o biodisponibilitate a substanţei medicamentoase îmbunătăţite. S-au preparat amestecuri polimerice de chitosan (0,3%), un polimer sensibil la variaţia de pH, şi poloxamer 407 (12%, 15%, 18%), polimer cu proprietăţi termoreversibile, în care a fost încorporată bupivacaină clorhidrat (0,25%). Pentru acestea s-au evaluat: temperatura de gelifiere, udabilitatea, comportamentul reologic şi cedarea in vitro a substanţei active. Formularea conţinând 15% poloxamer 407 s-a transformat într-o dispersie coloidală la 35°C, temperatura de la suprafaţa oculară. Valorile unghiurilor de contact pentru sistemele coloidale la temperatura fiziologică (35°C) au fost mai mici decât cele corespunzătoare formulărilor la temperatura nefiziologică (25°C), fapt ce indică o etalare corespunzătoare pe suprafaţa oculară. Studiile reologice au arătat un comportament pseudoplastic, iar la creşterea concentraţiei de poloxamer s-a înregistrat creşterea vâscozităţii preparatelor. Cedarea in vitro a bupivacainei clorhidrat din sistemele coloidale s-a realizat în conformitate cu modelul Higuchi. Dispersiile coloidale de chitosan şi poloxamer 407 pot reprezenta alternative viabile de creştere a biodisponibilităţii bupivacainei clorhidrat în anestezia topică oculară.

Chitosan and its Derivatives for Ocular Delivery Formulations: Recent Advances and Developments

“…Irimia et al have reported in situ gelling P407/CS formulations for the ocular delivery of bupivacaine hydrochloride, which is used as a topical anesthetic [235]. A series of P407/CS dispersions with various poloxamer concentrations were prepared by the "cold method".…”

Preliminary Study Regarding the Formulation and Physical Evaluation of Some Biocompatible, Oil in Water Microemulsions With Salicylic Acid for Dermatologic Use

“…Rheological evaluation was performed for the most representative systems, offering information concerning the phase behaviour, the quality profile and the flow characteristics according with their composition. Thus, MEAS 1 -MEAS 3 microemulsions were evaluated at 23 ± 0.5°C using Multi Visc rheometer (Fungilab SA, Barcelona, Spain), equipped with an LCP spindle, as it was previously reported [26].…”

Rho-Kinase Inhibitors – A New Broad-Spectrum Treatment in Ophthalmic Diseases. A Review

“…The recommended dose for Ripasudil 0.4% is one drop twice a day in the long term for patients with glaucoma or intraocular hypertension. According to specialized studies to date it has been observed that the drug administered alone decreases IOP by about 3.5 mmHg (2.6 mmHg -3.7 mmHg), administered in combination with a prostaglandin analogue decreases the additional IOP by approximately 3.2 mmHg and when supplemented with a beta-blocker treatment decreases the IOP by approximately 2.9 mmHg in addition [20,[36][37][38][39]92]. The side effects of Ripasudil documented in the literature were: blepharitis, allergic conjunctivitis, conjunctival hyperaemia and punctate keratitis, transient symptoms that appear to have been dose dependent.…”