Design and Evaluation of Propranolol Loaded Bio Flexi Ocusert Using Cocos Nucifera Biopolymer

The eye as a portal for drug delivery is generally used for local therapy against systemic therapy in order to avoid the risk of eye damage from high blood con-centrations of the drug, which is not intended. The unique anatomy, physiology and biochemistry of the eye render this organ impervious to foreign substances, thus presenting a constant challenge to the formulator to circumvent the protective barriers of the eye without causing permanent tissue damage.  Most ocular treatments like eye drops and suspen-sions call for the topical administration of ophthalmical-ly active drugs to the tissues around the ocular cavity. These dosage forms are easy to instill but suffer from the inherent drawback that the majority of the medication they contain is immediately diluted in the tear film as soon as the eye drop solution is instilled into the cul-de-sac and is rapidly drained away from the precorneal cavity by constant tear flow and lacrimo-nasal drainage. Therefore, only a very small fraction of the instilled dose is absorbed by the target tissue for this reason, concentrated solutions and frequent dosing are required for the instillation to achieve an adequate level of therapeutic effect. One of the new classes of drug delivery systems, ocular inserts, which are gaining worldwide praise, release drugs at a pre-programmed rate for a longer period by increasing the precorneal residence time Propranolol is a sympatholytic non-selective beta blocker. Sympatholytic are used to treat hypertension, anxiety and panic and glucoma. It was the first successful beta blocker developed. Propranolol is rapidly and completely absorbed, with peak plasma levels achieved approximately 1–3 hours after ingestion. The main metabolite 4-hydroxypropranolol, with a longer half-life (5.2–7.5 hours) than the parent compound (3–4 hours), is also pharmacologically active. Propranolol is a highly lipophilic drug achieving high concentrations in the brain. Propranolol is a non-selective beta blocker, that is, it blocks the action of epinephrine and norepinephrine on both β₁- and β₂-adrenergic receptors. It has little intrinsic sympathomimetic activity (ISA) but has strong membrane stabilizing activity. Coconut is highly nutritious and rich in fiber, vitamins, and minerals. It is classified as a "functional food" because it provides many health benefits beyond its nutritional content It is also a very good source of B-complex vitamins such as folates, riboflavin, niacin, thiamin, and pyridoxine. These vitamins are essential in the sense that body requires them from external sources to replenish.  Coconut meat and water contain a very good amount of potassium. 100 g of fresh meat contains 356 mg% or 7.5% of daily required levels of potassium.

MATERIALS AND METHODS

Material- coconut bio-polymer were collected.

I. Preparation of Ocuserts

The various formulations of bio flexi ocusert were prepared by solvent casting method. Different bio-flexi ocusert (1:1 to 1:10) were prepared with varying concentration of the biopolymer. Biopolymer was taken in mortar pestle and triturated properly for the fine powder. After that 50 mg of dextrose & 50mg of glucose was added along with 100 mg of nanosized drug (propranolol). Then 10 ml of distill water was added and triturated properly in uniform direction. After that magnetic stirring was done for 45 minutes and sonication was performed (3cycle). After that the mixture was uniformly spreaded on a petri-dish and dried at room temperature. Bio-flexi film was obtained.

Formulation detail

Flowchart-

EVALUATION PARAMETER-

The ocuserts were evaluated for thickness, folding endurance, drug content uniformity, surface pH, and in-vitro diffusion studies

Thickness- Insert thickness was measured by a Vernier caliper at five different points on the film. The mean thickness and standard deviation (SD) were calculated.

Weight uniformity - Weight uniformity of bio-flexi ocusert determined by taking weight of ten bio- flexi ocusert of sizes 1 square cm diameter from every batch and weight individually on electronic balance. The avg. weight was calculated.

Folding Endurance- Folding Endurance of the film was determined by repeatedly folding the inserts at the same place till it breaks. The ocuserts was folded in the center, between finger and thumb and then opened. This was one folding. The number of times, the film could be folded at the same place without breaking gave the value of folding endurance

Drug content uniformity- Uniformity of drug content was determined by assaying the individual inserts. Three inserts from each batch were powdered individually and each was dissolved in 100 ml of purified water by stirring on a magnetic stirrer for 2 hours. The absorbance of each of these solutions was then measured on UV-visible spectrophotometer at 290 nm.

In-vitro diffusion studies the in-vitro drug release studies were carried out using diffusion cell. 0.7 ml of isotonic phosphate buffer of pH 7.4 was placed in the donor chamber, which acted as tear fluid. Ocusert was placed in the donor compartment over a egg shell membrane. 25 ml of isotonic phosphate buffer was taken as the receptor medium and the apparatus was maintained at 37° ± 2° C and was continuously stirred using magnetic stirrer. The samples were withdrawn at regular intervals and analyzed at 290 nm.

Figure- Invitro drug release of propranolol ocuser