Preparation and Evaluation of Olanzepine Microsphere for Treatment of Depression and Obessive Compulsive Disorder

M. T. Deshmukh¹*, M. R. Ghante², T. V. Deshmukh³, V.T. Deshmukh⁴

¹Department of Pharmaceutics, Smt. Kashibai Navale College of Pharmacy, Kondhwa, Maharshtra, India.

²Department of Pharmaceutics, Department of Pharmaceutical Chemistry,

Smt. Kashibai Navale College of Pharmacy, Kondhwa Maharshtra, India.

³Department of Pharmaceutics, Shivnagar Vidya Prasarak Mandals,

College of Pharmacy Malegaon BK, Baramati maharshtra, India

⁴Department of Pharmaceutics, Meruling Shikshan Sansthas’s College of Pharmacy, Jawalwadi, Medha.

*Corresponding Author E-mail: madhuripharmacist9@gmail.com

ABSTRACT:

The clinically important dopamine receptor employed in schizophrenia was proven to be the source of the second generation atypical antipsychotic medication that was licensed in UA in 1996. However, less than 60% of it is absorbed due to considerable first-pass metabolism. The goal of this research was to create a microsphere of Olanzapine in order to increase its bioavailability and prevent hepatic first pass metabolism. Different concentrations of sodium alginate and carbopol polymer were used in a factorial design. They were assessed test like Porsolt swim, tail suspension, elevated plus maze, and tail suspension test in animals (Wistar albino rats and mice) in order to assess the effectiveness of antidepressants. The result showed a considerable reduction in immobility duration when compared to group I (normal).An optimized batch study using wistar rats was conducted to assess the antidepressant impact of administering Olanzapine microsphere over A.P.I.

KEYWORDS: Antidepressant Activity, Microsphere, Dopamine, ionic gelation.

INTRODUCTION:

Depression is common disease affecting millions of people worldwide. A tragic fatality associated with loss of life every year because of depression. It is a common mental disorder. It involves a depressed mood or loss of pleasure or interest in activities for long periods of time^{. 1-4}Olanzapine is antipsychotic agent having problems of low water solubility and higher lipid solubility resulting different oral bioavailability. Olanzapine maintain balance levels of dopamine and serotonin in brain and used in bipolar disease. Olanzapine having poor aqueous solubility and undergo first pass metabolism hence poor bioavailability problem.

To overcome this problem microsphere of Olanzepine formulated using combination of alginate and carbopol polymer increase bioavailability for treating depression and depression related symptoms.^5,6

MATERIALS AND METHODS:

Chemicals:

Olanzapine, Carbapol 974P, Sodium alginate, Ca. chloride.

Method of preparation:

Method of preparation: Sodium alginate polymer and carbapol were used in the ionic gelation process to prepare Olanzapine microspheres. A polymer solution is prepared by magnetically swirling a mixture of sodium alginate and carbapol in mildly heated deionized water. Olanzapine and polymeric solution were dispersed using a 30 minute sonication technique. Using a hypodermic needle, the formed dispersion was then gradually added to the calcium chloride solution. The microspheres that had formed were filtered, repeatedly cleaned, and vacuum-dried ⁷.

Experimental design:

In order to test the in-vivo antidepressant efficacy, three groups of rats of either sex each were used: the control group, the pure medication treatment group, and the microsphere formulation group. The animals had access to food and water on demand as well as housing with artificial lighting made of polypropylene to promote the day-night cycle.

Antidepressant evaluation test:

1. Porsolt swim test:

The test was utilized to assess the anti-depressant efficacy of the optimized formulation. Rats of either sex were used in individual tests by being placed in big glass cylinders with water that was about 30cm deep. The water level in the beaker should be such that the rat cannot reach the bottom or escape. On the first day of test rat kept in the cylinder for 15 minutes and then it is tested again for 5 minutes 24hours later. Both the amount of time spent striving and the latency to float are assessed^8,9.

2. EPM test:

EPM test is use to determine anxiety like behavior by using the elevated plus maze apparatus.The apparatus consist of 2 open and 2 closed arm. Rats and mice can use the same procedure, but with a correspondingly larger apparatus (rats: 110 x 50 x 40cm, and mice: 80 x 35 x 15cm). An anxiety-like state is characterized by duration and frequency of entries into open and closed arms.

3. Tail suspension test:

This behavioral test is helpful in determining potential of antidepressant medication. Mice is suspended by their tails using tape. So that mice are unable to move or cling to objects around. This test usually lasts six minutes. Animal was considered to be immobile when it did not show any movement of the body.^10,11

RESULT AND DISCUSSION:

Optimized formulation selected was no.9 formulation based on % yield, entrapment capacity, release rate and mucoadhesion study

In-vivo Study:

Wistar rats were used in an optimized batch trial to determine the antidepressant effect following dosing of 72mg of Olanzapine microsphere. (same as 5mg of A.P.I.)

Table 1: Formulation code

Ingredient	Formulation no.
Ingredient	1	2	3	4	5	6	7	8	9
Olanzapine API (mg)	200	200	200	200	200	200	200	200	200
Polymer: Sod. alginate and carbopol	4	5	6	4	5	6	4	5	6
Calcium chloride (gm.)	1	1	1	1.5	1.5	1.5	2	2	2
Vehicle (Distill water)	100	100	100	100	100	100	100	100	100

Table No.2: Swimming Time (Olanzapine 10mg/kg, i.p.)

Time (minute)	Normal		Standard		Carbopol
Time (minute)	Average	S.E.M.	Average	S.E.M.	Average	S.E.M.
15	139.3333	6.437736	175.8333	6.630317	176.500	9.454276
30	152.6667	6.785605	168.1667	6.305641	213.500	25.19491
60	146.6667	9.690774	166.3333	7.278584	227.6667	9.25803

Figure 1: Porsolt swim test

1. Effect of swimming:

In comparison to the animals in the control group, all treatment animals exhibited a significant reduction in the amount of immobile time and the animals treated with carbopol formulation showed better activity.

Elevated Plus Maze:

Time spent by the animals in open arm was significantly increased as compare to normal group indicating the anti-depressant effect of all formulations. Time spent by the animals in the closed arm was significantly decreased in all treatment groups clearly indicating the anti-depressant activity.

Treatment

Observations

Duration of the open arm (s)

open arms entries

(no.)

Duration of closed arm (s)

closed arms entry (no.)

Normal (Saline)

139.67±

1.81

4±

1.21

238.67±

2.37

22.33±

2.51

Std (Olanzepine)

209.67±

2.19

7.67±

1.79

155.00±

2.60

10.00±

0.57

T- 1 (Carbopol)

209.34±

1.56

12.00±1.61

177.00±

1.72

8.67±

1.20

Figure 3: Time spent in open and close arm entries

Tail-Suspension Test:

Immobility time of animal was significantly reduced after receiving the appropriate treatment, suggesting the formulation's antidepressant effect; the mice treated with chitosan showed greater activity.

Treatment	Observations
Treatment	Time Spent Immobile (Prior)	Time Spent Immobile (After)
Normal	115.84±2.157	120.50±2.985
Olanzapine (Std)	118.00±1.907	56.84±2.552
T 1 (Carbopol)	141.67±2.270	48.34±1.216

Figure 4. Tail suspension test

DISCUSSION:

Depression defined by mood fluctuations, pessimism, decreased physical activity, and a helpless sense. Changes in the brain's monoamine levels, such as those of dopamine, noradrenaline, and serotonin, are thought to be the cause. Therefore drug that either inhibit monoamine oxidase or block the reuptake of these neurotransmitters could be utilized to treat depression by increasing the lower amounts of these monoamines in the brain.

CONCLUSIONS:

It was concluded that in comparison to the pure API, it was determined that the produced olanzapine microsphere exhibited good efficacy in antidepressant action.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

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Received on 29.04.2024 Revised on 21.08.2024

Accepted on 30.10.2024 Published on 27.03.2025

Available online from March 27, 2025

Research J. Pharmacy and Technology. 2025;18(3):1189-1191.

DOI: 10.52711/0974-360X.2025.00172

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