Optimisation of HPMC ophthalmic inserts with sustained release properties as a carrier for thermolabile therapeutics

Abstract

A methodology was developed and optimised for the preparation of a new drug delivery system (DDS) with sustained release properties to allow ocular protein delivery and to limit destructive production steps during manufacturing. Elevated temperatures, shear forces and an oxidative environment should be avoided in order to prevent denaturation or oxidation of proteins. An aqueous HPMC solution was prepared using heat and casted into small semi-rod-shaped PVC blisters. The polymer solution was allowed to cool down and was partially dehydrated at room temperature. A drug solution containing glycerol, drug and water was subsequently added to rehydrate the partially dehydrated polymer matrix at a temperature of 2°C. Several parameters of the production process were varied to determine their influence on the release kinetics from HPMC inserts from three different molecules of different molecular weight. This production method was further optimised in order to shorten the rehydration time from weeks to days, while eliminating heat and shear forces on the selected drug molecules sodium fluorescein, lysozyme and albumin. Slow release kinetics were achieved for sodium fluorescein and lysozyme as model drug molecules. The higher molecular weight of albumin prevented a good penetration into the insert during the rehydration process resulting in predominantly burst release. The biocompatibility of a viscous HPMC solution was evaluated on SV40-human corneal epithelial cells with PrestoBlue and no cytotoxic effects were observed.

Polysaccharides in Ocular Drug Delivery

“…Ophthalmic inserts containing cellulose-based polymers are extensively described in the literature [82]. Ethylcellulose, a hydrophobic polymer, can be incorporated into the formulation to decrease insert deformation and blurred vision [97], but these insoluble inserts must be removed from the eye after drug release. Film forming properties and biocompatibility of cellulose ethers makes them a good excipient for modifying ocular insert properties.…”

Development of a topical tissue cross-linking solution using sodium hydroxymethylglycinate (SMG): viscosity effect

“…Even though SMG is smaller in size than a typical nanocrystal (∼300 Da), it is possibly being released from the polymer in a similar manner. HPMC has been used to make ophthalmic inserts and films, which could be a possible method for our formulation to be applied [40,41]. Using an ointment is by far the most cost-effective solution, but an insert or a film would increase contact time, hence increase bioavailability and stability of the drug more efficiently.…”

A Review about various Nanomaterials in Drug Delivery Systems and their Applications

“…They could be prospective delivery methods to lessen the intraocular pressure and to encourage neuroprotective possessions in glaucomatous patients [72]. Everaert et al, (2017) prepared and optimized HPMC based ocular inserts with sustained release properties as carriers for thermolabile medicaments. Sodium fluorescein and lysozyme were selected as model drugs to attain the slower drug release kinetic.…”

“…Primarily burst release was produced in the process of rehydration due to low penetration into the insert because of HMW albumin. SV40-human corneal epithelial cells with PrestoBlue ® were selected for evaluation of biocompatibility of a viscous HPMC solution, negligible cytotoxic reactions were detected [76]. Lee et al, (1999) formulated and evaluated ocular inserts comprising tropicamide and phenylephrine.…”