Abstract
The aim of this study was the development and optimization of chitosan and hydroxypropyl methylcellulose (HPMC) in situ gelling systems, loaded with bupivacaine hydrochloride for topical ocular administration. This study is based on the properties of two polymers: chitosan, which has mucoadhesive action and is a pH-sensitive polymer, but also the cellulose derivative hydroxypropyl methylcellulose, a thermosensitive polymer which has mucoadhesive properties and increases the viscosity of systems. The analysis and optimization of in situ gelling systems were performed based on an experimental design and response surface methodology. The following formulation parameters were considered: X1 = chitosan concentration (0.5%, 1%), X2 = HPMC E 5 LV concentration (2%, 5%) and X3 = Chitosan/HPMC E 5 LV ratio (1/1, 2/1). In addition, the parameters to be optimized were represented by the contact angle (CA (°)), viscosity and cumulative percentage of bupivacaine hydrochloride released in vitro. The results indicate that the designed in situ gelling systems are suitable for bupivacaine prolonged ophthalmic release and overcome the principal disadvantages of the liquid’s ocular formulations. An immediate therapeutic effect corresponding to ocular anesthetic installation was assured in the first stage: burst bupivacaine release. In the second phase, the gradual drug release was assured for over 6 h. This drug release profile, together with the corresponding rheological profile and a collection of superficial properties for good ocular adhesion balanced with an adequate hydrophilic character, assured the desired quality of the attributes for the proposed systems. The system, based on chitosan 1%, HPMC E 5 LV 5% and a 1/1 polymer ratio, could be a solution for the proposed formulation of in situ gelling colloidal systems, since the viscosity of the system was within the range of the optimal viscosity of the eye, and the amount of bupivacaine hydrochloride released after 6 h was the highest at 69.55%.
Highlights
The human eye is a complex system, so the administration of drugs to the eye is in continuous research
Polymer mixtures of chitosan and hydroxypropyl methylcellulose (HPMC) E 5 LV were prepared by varying the concentration and ratio of the polymers in order to increase the ocular bioavailability of bupivacaine hydrochloride
The aim was to formulate ophthalmic systems with in situ gelling in order to increase the ocular bioavailability of bupivacaine hydrochloride by combining chitosan, a pH-sensitive and mucoadhesive polymer, with HPMC E 5 LV, a thermosensitive polymer with the property of increasing the viscosity, with lubricating and mucoadhesive actions
Summary
The human eye is a complex system, so the administration of drugs to the eye is in continuous research. Certain systems may cause discomfort to the patient in the eye system, and in some situations, the method of administration is invasive. Topical ocular administration is a simple method that can be performed at home without the need for medical care, improving patient adherence to the treatment [1]. Chitosan is a biopolymer with many useful properties for ophthalmic use; it is biocompatible, biodegradable, non-toxic and has its own antibacterial and antifungal actions [6]. It has some limitations that are mainly due to its low solubility and low mechanical strength of the gels obtained from it due to the lack of control over the pore size of the network and the toxicity of crosslinking agents, respectively [8]. The mechanical strength of chitosan gels can be improved by being combined with other polymers [9]
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