INTRODUCTION:

The eye as a portal for drug delivery is generally used for local therapy against systemic therapy to avoid the risk of eye damage from high blood concentration 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 opthalmic treatments like eye drops and suspensions call for the topical administration of opthalmic active drugs to the tissues around the optical cavity^1-3.

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 lacrima-nasal drainage. Therefore, the targeted tissues absorb a very small fraction of instilled dose. For this reason, concentrated solutions and frequent dosing are required for the instillation to achieve an adequate level of curative effect^4-7.

Conventional ophthalmic preparation shows the poor bioavailability and therapeutic response due to pre-corneal constraints. Development of novel ophthalmic formulation provides better therapeutic efficacy by prolonging the drug release and prolonged contact time with the corneal surface. Ocusert is the new drug-delivery systems which are designed in such a way that they release the drug at the predetermined rate thus eliminating the frequent administration of the drug⁸.

Ofloxacin has a broad antimicrobial spectrum against gram-positive and gram-negative microorganisms. This drug is routinely used in the many ocular conditions like infections, inflammations, conjunctivitis, blepharitis, iritis, corneal ulcer, bacterial keratitis⁹, etc. It is presently available as an eye drops 0.3%. It is administered 1-2 drop into the affected eye every four hours¹⁰. So in the present delivery system, we aimed to find the right ratio of polymer to control the rate of release of Ofloxacin from ocuserts.

MATERIAL AND METHODS:

Preparation of ocular inserts:

The ocular inserts wear prepared by solvent casting method. The inserts were prepared by solvent casting method. The required quantity of the polymer PVA in a different ratio (100,150,200,250,300,350,400 mg) was weighed and dissolved in distilled water by gentle stirring. The Glycerol (10% solution in distilled) was added as plasticizer to above solution under stirring condition. The required quantity of Ofloxacin (100 mg) is dissolved in sodium hydroxide (0.1N, 2ml) and added in polymer solution and Stirred 30 minutes to get a similar dispersion. After complete mixing, the casting solution was poured into clean petridish, and covered with an inverted funnel to allow slow and uniform evaporation at room temperature. The petridish was dried at room temperature for 24 hr. The dried films thus obtained were cut into circular pieces (10 mm) by the help of cork borer and stored until used^11,12. The composition of different formulation of Ofloxacin is given in table 1.

Evaluations of prepared formulations

Uniformity of weight:

For determination of ocular inserts uniformity, twenty ocular inserts were taken from each batch and different areas of the film and weighed individually on electronic balance. Mean weight of inserts of each formulation was recorded. The mean were then calculated.

Content uniformity:

To check the uniformity of the drug in the circular film, five ocular inserts were taken out from each film. Each inserts were then placed in beaker containing 10 ml of isotonic phosphate buffer pH 7.4 and dissolved and were filtered into 25 ml volumetric flask and the volume was made up to the mark with phosphate buffer. One ml of the above solution was withdrawn and the absorbance was measured by UV-VIS spectrophotometer at 288 nm with against blank.

Surface pH:

Surface pH of the inserts was determined by allowing them to swell in a closed Petri dish at room temperature for 30 min in 0.1 ml of distilled water. The swollen devices were removed and placed on Pen pH meter to found surface pH.

Swelling index:

Three films were weighed and placed separately in beakers containing 4 ml of distilled water. At regular intervals of time (every 10 min), the films were removed and the excess water on their surface was removed using a filter paper and then again weighed. The procedure was continued till there was no increase in the weight. The ocular inserts was swelled and increased in the weight at 50 minutes. The swelling index was then calculated by using formula.

Swelling Index (S_w) %= [w_t - w_o/w_o] ×100

(S_w)%= equilibrium percent swelling, w_t: weight of swollen insert after time t, w_o: original weight of insert at zero time

% Moisture absorption:

The prepared ocular inserts was accurately weighed and placed in a desiccators containing aluminium chloride it was kept for 3 days. The ocuserts was taken out and reweighed after 3 days. The amount of moisture absorbed by the ocular inserts was calculated by using the following formula⁶².

% Moisture loss:

The films were weighted and kept in desiccators containing anhydrous calcium chloride. After three days, the films were taken out and reweighed. The percentage moisture loss was calculated using the following formula⁵⁴.

In-vitro diffusion study:

Static Franz glass diffusion cells have been used in order to evaluate the release profile. These cells consist of donor and acceptor chambers between which a diffusion membrane is positioned. Cellulose nitrate membranes used with an average pore size of 0.1 μm were used. The study was carried out in 50 ml of Phosphate buffer solution (7.4 pH). The dissolution medium was maintained temperature at 37±0.5^oC. At predetermined time intervals 1 ml of sample were withdrawn and replaced with fresh media. The The sample was analyzed for the drug content using UV spectrophotometer at 288 nm^13-17.

RESULT AND DISCUSSION:

The ocular inserts of Ofloxacin were prepared by solvent casting technique and distinguished on the basis physico-chemical characteristics, and in vitro release studies.

Table 1: Composition of Ofloxacin ocuserts

Ingredients	F₁	F₂	F₃	F₄	F₅	F₆	F₇
Ofloxacin	100 mg	100 mg	100 mg	100 mg	100 mg	100 mg	100 mg
PVA	100 mg	150 mg	200 mg	250 mg	300 mg	350 mg	400 mg
Glycerol	0.2 ml	0.4 ml	0.6 ml	0.8 ml	1.0 ml	1.2 ml	1.4 ml
Distilled water	10 ml	10 ml	10 ml	10 ml	10 ml	10 ml	10 ml

Table 2: Physicochemical evaluation of Ofloxacin ocular inserts

Formulations	F1	F2	F3	F4	F5	F6	F7
Weight variation	6.46±0.03	6.74±0.02	7.59±0.08	8.53±0.04	9.43±0.04	10.56±0.05	12.75±0.05
Thickness	0.182±0.02	0.236±0.02	0.334±0.03	0.413±0.01	0.482±0.01	0.525±0.01	0.541±0.02
% Moisture absorption	4.78±0.19	5.89±0.21	6.59±0.12	7.23±0.09	8.10±0.06	8.94±0.20	9.63±0.44
% Moisture loss	4.76±0.18	5.69±0.17	6.05±0.15	6.98±0.14	7.37±0.22	8.16±0.16	9.64±0.45
pH	6.73±0.06	6.76±0.05	6.83±0.06	6.80±0.1	6.76±0.12	6.90±0.06	6.96±0.43
% Drug content	69.98±1.70	73.67±4.72	75.68±4.62	77.32±4.86	71.29±4.55	73.96±5.60	72.46±5.59
% Swelling Index	8.24±0.24	10.51±0.16	11.59±0.09	14.26±0.12	16.73±0.07	19.18±0.16	22.52±0.08

All values were expressed as mean±S.D; number of trials (n) = 3

Table 3: In vitro drug release profile of ocular inserts

Time in Hours	% Cumulative Drug Release
Time in Hours	F1	F2	F3	F4	F5	F6	F7
1	37.3	31.2	24.6	19.1	11.2	9.7	5.3
2	59.6	51.7	41.3	38.3	26.3	17.3	10.5
4	72.4	65.1	55.5	50.4	35.8	28.2	22.4
6	82.3	79.8	68.3	60.7	52.7	39.7	35.7
8	91.5	88.3	79.3	74.2	67.4	57.6	51.5
10	99.2	95.1	87.4	84.9	79.2	70.1	64.2
12	-	99.7	93.2	90.4	84.3	79.5	73.8
14	-	-	100.0	100.0	95.3	89.5	82.3
16	-	-	-	-	100.0	98.3	90.5

The physicochemical evaluation data presented in table 2 indicates that the thickness of the ocular inserts films vary from 0.182±0.02 mm to 0.541±0.02 mm. Thickness of ocuserts slightly increased as the concentration of PVA increased. Each preparation displayed similar thickness with low standard deviation values ensuring the homogeneity of the films prepared by film casting method. Those being the case formulations were not thick enough to produce any irritation while placing and being in cul-de-sac.

The outcomes showed that weights of formulations were ranging from 6.46±0.03 mg to 12.75±0.05 mg for ocular inserts films. This reveals that there was no relevant weight diversity in all formulations.

The percentage moisture absorption and moisture loss was also influenced by polymer used in the insert preparation. The results indicate that the moisture absorption and moisture loss were varied from 4.78±0.19% to be 9.63±0.44% and 4.76±0.18% to 9.64±0.45% respectively. Increment in amount of PVA in formulation raised swelling, which may be due to its solubility in water. The moisture absorption was carried out to check the physical stability or integrity at wet condition. The percentage moisture loss was carried out to check the integrity of the film at dry condition.

Each of the formulations was subjected to assess the surface pH. They possessed pH near to neutral pH and hence will not produce any difficulty or irritation while placing in the cul-de-sac of the eye. The results showed that percentage swelling index of formulations were ranging from 8.24±0.24 to 22.52±0.08for ocular inserts films. This reveals that increase in amount of PVA in formulation raised in percentage swelling index of ocular insert. For the various formulations drug content uniformity was found to vary between 69.98±1.70% to 77.32±4.86%. The formulation F1 showed least drug content (69.98±1.70).

At different time interval sample was withdrawn and cumulative percentage drug released in mg was calculated, on the basis of mean amount of Ofloxacin present in the respective films (table-3). Formulation F5 showed a maximum cumulative percentage drug release of 100.0% at the end of 16 hours, followed by the other formulations F6 (98.3 %) and F7 (90.5%). While the formulations F1, F2, F3 and F4 release maximum drug before 14 hours. From the result it was observed that formulation F5 shows good physicochemical parameters as compared to other formulations. As results indicated that the % cumulative release for ocular insert F5 was 100% at the end of 16 hours and hence found to be appropriate for therapy. Ocuserts can be converted to a promising marketable product in the category of ophthalmic products.

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Received on 04.11.2012 Modified on 11.11.2012

Research J. Pharm. and Tech. 5(12): Dec. 2012; Page 1497-1499