Development and Optimization of Chitosan-Hydroxypropyl Methylcellulose In Situ Gelling Systems for Ophthalmic Delivery of Bupivacaine Hydrochloride

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%.

Insights from a Box–Behnken Optimization Study of Microemulsions with Salicylic Acid for Acne Therapy

“…Rheological evaluation of microemulsions, along with the estimation of the hydrodynamic diameter of particles and an extensive superficial analysis oriented through quantification of adhesion properties, involved special attention by implementing a response surface methodology to follow and outline optimal systems as was reported in a couple of studies oriented to topical formulations design [67,85].…”

“…The internal structure of the systems and their stability can be evaluated by the measurement of γ L/G . Subsequently, the study of contact angle-CA at the contact with planar surfaces constitutes a method to evaluate the wettability of a system, particularly hydrophilicity or hydrophobicity nature, as it was reported in the study of Popa L. et al [85]. Goniometry was rarely applied in the research of microemulsions, and it was considered that their behavior at the contact with surfaces is not fully unveiled [100].…”

“…A rheological evaluation was performed for each microemulsion, with respect to phase behavior and flow characteristics as a function of internal composition based on the formulation factors involved. MELSA 1-MELSA 13 microemulsions were analyzed at 25 ± 0.5 • C, using Multi Visc Rheometer (Fungilab, Barcelona, Spain), equipped with an LCP spindle, as previously reported [57,85]. Viscosity measurements were performed by applying a rotation speed between 0.3-60 rpm, corresponding to a shear rate between 0.36 and 73.38 s −1 .…”

“…Drops of each sample (µL) were applied on microscope slides, captured with a digital camera, and measured over a period of 64 ms by an automated curve-fitting program. Young equation (Equation (3)) was fitted with two models of analysis: the pendant drop and contact angle models [85]:…”

Molecular Mapping of Antifungal Mechanisms Accessing Biomaterials and New Agents to Target Oral Candidiasis

“…Chitosan possesses essential properties related to drug delivery, specifically mucoadhesion promotion and the increase in drug penetration. It has a biodegradable character, the ability to be integrated in complex polymeric drug delivery systems, hydrogels, and nanocolloids, and not least, it presents regenerative and antimicrobial qualities [ 216 ]. Although these properties seem to describe an ideal structure for biomedical applications, chitosan needs proper processing due to its hydrophilicity and limited solubility [ 198 , 216 ].…”