Formulation and Development of Newer Aripiprazole Immediate Release Tablets

 

Poonguzhali Sathish Kumar¹*, Subal Chandra Basak¹, Sitty Manohar Babu²

¹Department of Pharmacy, Annamalai University, Chidambaram, 608002, Tamil Nadu, India

²Department of Pharmacology, SIMS College of Pharmacy, Guntur, 522001, Andhra Pradesh, India.

 

ABSTRACT:

Aripiprazole is an antipsychotic medication, works by changing the actions of chemicals in the brain. It is used to treat the symptoms of psychotic conditions such as schizophrenia and bipolar disorder (manic depression). In order to formulate a newer aripiprazole immediate release tablet of strength 30mg we evaluated the physical characteristics and the dissolution profile of the lab scale batch. The dissolution profile of the reference product and in house product was compared. The tablets from the lab scale batch were also subjected to accelerated stability studies. The results obtained were satisfactory and within the specified limits. In-vitro release profiles of the in-house product and reference product were similar. The lab scale batch tablets were found to be stable.

 

 

 

 

INTRODUCTION:

Aripiprazole is an antipsychotic medication, works by changing the actions of chemicals in the brain^{1, 2, 3}. It is used to treat the symptoms of psychotic conditions such as schizophrenia and bipolar disorder (manic depression)^4,5. Aripiprazole possess a different mechanism of action which is different from other FDA – approved atypical antipsychotics approved by Food and Drug Administration^{6, 7, 8}. Instead of acting as an antagonist at D₂ receptor it acts as a partial agonist at the D2 receptor^{9, 10}. It also acts as the partial agonist at the 5-HT₁A receptor but exhibits the role of the antagonist at 5-HT₂A receptor  similar to that of the other atypical anti-pshycotics¹¹.

 

Aripiprazole also possess high affinity towards 5-HT₇ receptor (acts as antagonist) and 5-HT₂C receptor (acts as a partial agonist) ^{12, 13}. Its action on the 5-HT₇ receptor and 5-HT₂C receptor is found to be the main cause of weight gain of the patient during the treatment period¹⁴. Aripiprazole also possess moderate affinity for histaminergic, α-adrenergic, dopaminergic receptors and serotonin transporter¹⁵. It has a very less affinity for muscarinic acetyl choline receptors¹⁶. The main aim and objective of this work is to perform the physical, chemical characterization (in-vitro dissolution profile) and accelerated stability studies for the optimized lab scale batch to formulate a stable and robust formulation of aripiprazole immediate release tablets of strength 30mg, which is used in the treatment of schizophrenia and bipolar disorders.

 

MATERIALS AND METHODS:

Physio-Chemical Characterization:

Based on the drug characterization study, drug-excipient compatibility study, and drug – excipient accelerated study data, the optimization of the manufacturing formula, manufacturing process and excipients was carried out^{17, 18}. Based on all the above studies a lab scale batch of aripiprazole immediate release tablets of strength 30mg was formulated (Table 1). Aripiprazole immediate release tablets of strength 30mg available in the market was used as the reference product.

 

Table1: Formula for the lab scale batch

 

For the above mentioned lab scale batch the physical characteristics and chemical characteristics (dissolution profile) were evaluated.

 

Accelerated Compatibility Study:

The formulated tablets (30mg) from the lab scale batch were packed in HDPE bottles and loaded in stability chambers for accelerated stability studies at 400C/75%RH. The required quantity of tablets in 400 C/75%RH were analyzed at the end of 1^st and 3^rd month for their physical appearance, assay, total impurity, water content and dissolution.

 

RESULTS:

Physio-Chemical Characterization:

The physical characteristics of formulated tablets and chemical characteristics (dissolution profile) were evaluated (Table 2 and 3).

 

Table 2: Physical characteristics of the lab scale tablets

 

Table 3: Chemical characteristics (dissolution profile) of the lab scale tablets

Accelerated compatibility study:

Table 4: Accelerated compatibility study data of lab scale batch tablets (30mg)

S. No	Condition	Initial	1Month	3Month
1	Description	Pale pink colored round shaped uncoated tablets	Pale pink colored round shaped uncoated tablets	Pale pink colored round shaped uncoated tablets
2	Assay (%w/w)	97.04	98.17	97.88
3	Water by KF (%w/w)	4.89	5.39	4.82
4	Dissolution (45min)	94.3	90.1	92.9
5	Total % of impurities	0.170	0.180	0.190

 

DISCUSSION:

From the above data (Table 2 and 3), it is evident that, all the physical and chemical characteristics were found to be satisfactory. In-vitro release profiles of the in-house product and reference product were similar. No significant changes in the analyzed characteristics were observed during the period of accelerated stability study. No significant variation in in-vitro dissolution study was observed between the reference product and lab scale batch tablets. From the study, it was inferred that the product is stable (Table 4).

 

 

CONCLUSION:

Based on the study results it may be concluded that the physical and chemical characteristics for the lab scale batch tablets was found to be similar with the reference product. The results of the accelerated stability data of lab scale batch tablets were found to be similar with the reference product. In conclusion the results of the lab scale batch study was found to be useful in the formulation development of newer aripiprazole immediate release tablets of 30mg.

 

ACKNOWLEDGEMENTS:

The authors are thankful to management of SIMS College of Pharmacy, Guntur, and Andhra Pradesh for providing the drug and other facilities required to carry out this research work.

 

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Accepted on 23.03.2017           © RJPT All right reserved