Archives of Applied Science Research

Formulation and Evaluation of Buprenorphine Sustained Release Buccal Tablets

Janagam Venkata Rajkumar^1*, Ravi Pratap Pulla¹, T. Kiran² and T. Shyam^{2 1}Department of Pharmacy, KVK College of Pharmacy,Abdullapurmet, India
²Department of Pharmacy, MRM College of Pharmacy, Telangana, India
^*Corresponding Author:
Janagam Venkata Rajkumar, Department of Pharmacy, KVK College of Pharmacy,Abdullapurmet, India, Email: janagam.raj@gmail.com

Received: 12-May-2023, Manuscript No. AASR-22-98661; Editor assigned: 15-May-2023, Pre QC No. AASR-22-98661 (PQ); Reviewed: 29-May-2023, QC No. AASR-22-98661; Revised: 17-Aug-2023, Manuscript No. AASR-22-98661 (R); Published: 24-Aug-2023

Introduction

Buprenorphine is a semisynthetic opioid that may offer an alternative to μ-opioid agonists. Buprenorphine exhibits partial agonism at μ-opioid receptors while maintaining a relative potency, compared with oral morphine, of between 75:1 and 115:1. In addition to partial agonism at μ-opioid receptors, buprenorphine is a κ-opioid receptor antagonist and appears to act as a “chaperone” ligand, increasing the expression of μ-opioid receptors on cell membranes [1]. It also has agonist activity at Opioid Receptor-Like 1 (ORL1) receptors that confers both an additive analgesic effect (through activation of receptors at the dorsal horn) and an inhibitory effect (through activation of receptors in the brain) [2]. Activation of these receptors also leads to blockade of the rewarding effects of morphine, which suggests that ORL1 receptors may contribute to the limited tolerance observed with buprenorphine [3].

Materials and Methods

Buprenorphine, HPMC K4M, HPMCK15M, Locust bean gum, MCC pH 102, magnesium stearate, talc all the chemicals were laboratory grade [4,5].

Formulation development of tablets: All the formulations were prepared by direct compression. The compositions of different formulations are given in Table 1. The tablets were prepared as per the procedure given below and aim is to prolong the release of buprenorphine. Total weight of the tablet was considered as 100 mg [6,7].

Procedure

1.Buprenorphine and all other ingredients were individually passed through sieve no ≠ 60.
2.All the ingredients were mixed thoroughly by triturating up to 15 min.
3.The powder mixture was lubricated with talc.
4.The tablets were prepared by using direct compression method [8,9].

Table 1: Formulation composition for tablets

Evaluation of post compression parameters for prepared tablets: The designed formulation tablets were studied for their physicochemical properties like weight variation, hardness, thickness, friability and drug content [10].

Results and Discussion

The present study was aimed to developing buccal tablets of buprenorphine using various polymers. All the formulations were evaluated for physicochemical properties and in vitro drug release studies (Table 2 and Figure 1).

Table 2: Observations for graph of buprenorphine in p H 6.8 phosphate buffer (255 nm)

Table 3: Pre-formulation parameters of powder blend

Analytical method: Graphs of buprenorphine as taken in buccal pH that is in p H 6.8 phosphate buffer at 255 nm (Table 3).

Tablet powder blend was subjected to various pre-formulation parameters. The angle of repose values indicates that the powder blend has good flow properties. The bulk density of all the formulations was found to be in the range of 0.43(gm/cm³) to 0.58 (gm/cm³) showing that the powder has good flow properties. The tapped density of all the formulations was found to be in the range of 0.57 to 0.69 showing the powder has good flow properties. The compressibility index of all the formulations was found to be ranging between 16 to 18 which show that the powder has good flow properties. All the formulations has shown the Hausner ratio ranging between 0 to 1.2 indicating the powder has good flow properties.

Quality control parameters for tablets: Tablet quality control tests such as weight variation, hardness, and friability, thickness, and drug release studies in different media were performed on the formulation of tablet (Tables 4 and 5).

Table 4: Post compression parameters

In-vitro quality control parameters for tablets: All the parameters such as weight variation, friability, hardness, thickness and drug content were found to be within limits (Figures 2-4, Tables 6 and 7).

Table 5: Dissolution data of buprenorphine tablets prepared with HPMC K4M in different concentrations

Table 6: Dissolution data of buprenorphine tablets prepared with HPMC K15M in different concentrations

Table 7: Dissolution data of buprenorphine tablets prepared with locust bean gum in different concentrations

In-vitro drug release studies

From the dissolution data it was evident that the formulations prepared with Methocel K4M as polymer were unable to retard the drug release up to desired time period i.e., 12 hours. Whereas the formulations prepared with Locust bean gum retarded the drug release in the concentration of 8 mg showed required release pattern i.e., retarded the drug release up to 12 hours and showed maximum of 98.54% in 12 hours with good retardation. The formulations prepared with Methocel 15 M showed more retardation even after 12 hours they were not shown total drug release. Hence they were not considered.

Application of release rate kinetics to dissolution data: Various models were tested for explaining the kinetics of drug release (Table 8). To analyze the mechanism of the drug release rate kinetics of the dosage form, the obtained data were fitted into zero-order, first order, Higuchi, and Korsmeyer-Peppas release model (Figures 5-8).

Table 8: Release kinetics data for optimized formulation

From the above graphs it was evident that the formulation F8 was followed Peppas order release kinetics.

Conclusion

The aim of the present study was to develop buccal formulation of buprenorphine to maintain constant therapeutic levels of the drug for over 12 hrs. Various grades of HPMC were employed as polymers. Buprenorphine dose was fixed as 8 mg. Total weight of the tablet was considered as 100 mg. Polymers were used in the concentration of 4 mg, 8mg and 12 mg concentration. All the formulations were passed various physicochemical evaluation parameters and they were found to be within limits. Whereas from the dissolution studies it was evident that the Formulation (F8) showed better and desired drug release pattern i.e., 98.54 % in 12 hours. It followed Peppas release kinetics mechanism.

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