Formulation Development of Antihypertensive Drug Labetalol HCL Injection

Guru Prasad, A L (2019) Formulation Development of Antihypertensive Drug Labetalol HCL Injection. Masters thesis, C.L.Baid Metha College of Pharmacy, Chennai.


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Labetalol Hydrochloride Injection USP (Labetalol hydrochloride) is an adrenergic receptor blocking agent possessing both alpha1 (post-synaptic) and beta-receptor blocking activity. Its action on beta-receptors is four times stronger than that on alpha-receptors. It antagonizes beta1- and beta2-receptors equally. The ratios of alpha- to beta-blockade differ depending on the route of administration estimated to be 1:3 (oral) and 1:7 (IV). Onset of action- Oral: 20 minutes to 2 hours; IV: Within 5 minutes. Peak effect: Oral: 2 to 4 hours; IV: 5 to 15 minutes. Duration of action- Oral: 8 to 12 hours (dose dependent), IV: Average: 16 to 18 hours (dose dependent). Half-Life Elimination -Oral: 6 to 8 hours; IV: ~5.5 hours. The parenteral route of Labetalol hydrochloride is considered as the best choice of route than compared to the oral route. In this introduction chapter discussed about parenteral dosage form, its significance, hypertension, mechanism of alpha beta blockers, advantages and disadvantages, different routes of administration, formulation of parenteral dosage form, evaluation of parenteral along with sterilization technique. And also briefly discussed about Preformulation studies of parenteral medications. The literature related to this work was surveyed and a brief discussion had been given on each literature in this chapter. The objective of the present formulation development was to develop a pharmaceutically acceptable, stable and reproducible generic formulation of Labetalol hydrochloride injection. The development studies were aimed at developing a drug product formulation matching the RLD (Reference listed drug) drug product characteristics and complying to the product characteristics listed in the USP monograph for of Labetalol hydrochloride injection. The method chapter covers the details of experimental methods, including Preformulation study, compatibility study, stress study along with evaluation study and finally stability study. The result chapter depicts the results for the all tests indicated in the method chapter. The results for all the parameter to be evaluated for the prepared of Labetalol hydrochloride injection and the Stability of the prepared formulation were given in this chapter. The discussion chapters deal with the optimization of the process and four formulation trials were taken for the optimization of process variables. The best trial was considered for further batches. The tests included in the study were performed with optimized batch and for each test separate batches were taken and study was conducted. The compatibility study with the containers, filters and tubings were tabulated. The prepared formulation was subjected to stress study with oxygen sensitivity, pH extremities, freeze thaw and photo stability and the results were found to be within the specification limits. Evaluation is the necessary step for parenteral and the solution to be injected should be free from any particulate matter to provide the sterile dosage form. The prepared injection provides all the compatibility for the quality control tests and found to be sterile. The prepared of Labetalol hydrochloride injection was assured for stability and it passes the stability criteria for that particular injection. The samples were analysed after withdrawal of the sample from stability chamber and all the test parameters was carried out accordingly and the sample passes all the test criteria and the results was found to be within specification. Labetalol is a unique parenteral that competitively blocks alpha- and beta-adrenergic receptors. The main objective of the study was to formulate a safe and stable Labetalol Hydrochloride Injection USP (labetalol hydrochloride) with the dose of 5 mg/ mL. Drug, methyl paraben, propyl paraben, EDTA, dextrose, order of mixing was determined in pre-formulation development. Based on D-value, moist-heat sterilization method (121°C for 20 mins) is chosen for the developed injection formulation. The Process compatibility study reveals that injection potency and purity did not affected when exposed to stainless steel and process tubing. The filter compatibility study demonstrates that the Labetalol Hydrochloride Injection passes through filter without having drug loss due to binding of the drug to the membrane. Stability study of developed formulation conducted at Nitrogen purged environment, different pH, and various temperatures are tested over time for the amount of drug, methylparaben, propylparaben, EDTA, impurities, and particulate matter clearly indicated the drug product was stable. Labetalol Hydrochloride injection passes the entire quality control release test and there were no mechanical issues during the process. Thus, the product can be manufactured at a large scale.

Item Type: Thesis (Masters)
Additional Information: 261710006
Uncontrolled Keywords: Antihypertensive Drug, Labetalol HCL, Injection
Subjects: PHARMACY > Pharmaceutics
Depositing User: Ramakrishnan J
Date Deposited: 23 May 2022 06:01
Last Modified: 23 May 2022 06:01

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