Formulation and Evaluation of Sustained-Release Matrix Tablets of Bethanechol Hydrochloride

Bethanechol Hydrochloride is a direct-acting Para sympathomimetic agent prescribed for urinary retention and gastrointestinal atony. Its short half-life necessitates frequent dosing, leading to poor patient adherence. Sustained-release (SR) matrix tablets are an effective strategy to maintain therapeutic concentrations over an extended period. Hydrophilic polymers such as HPMC swell and form a gel layer that controls diffusion, while hydrophobic polymers regulate erosion and permeability. This study focuses on designing an SR matrix system capable of once-daily administration

Chemical name: 2-[(Aminocarbonyl)oxy]-N, N, N-trimethyl-1-propanaminium chloride

Molecular formula: C?H??ClN?O?

Molecular weight: 196.68 g/mol

Category: Parasympathomimetic (Cholinergic agonist)

Structure:

Figure 1: The Bethanechol Hydrochloride.

Matrix systems regulate drug release through mechanisms such as diffusion, erosion, swelling, or a combination of these processes. Hydrophilic matrices (e.g., HPMC) absorb water to create a gel layer that controls the diffusion of the dissolved drug; as the outer layer erodes or becomes increasingly porous, the release continues. Hydrophobic matrices (e.g., ethylcellulose) depend on restricted water penetration and complex diffusion pathways to slow down the release. The integration of hydrophilic and hydrophobic polymers can offer complementary mechanisms to stabilize release rates and reduce burst effects.

Figure 2: A regular release product and sustained release drug plasma drug concentration

METHOD DEVELOPMENT

Matrix tablets of Bethanechol HCl were prepared by “direct compression method”. All ingredients were accurately weighed and sieved through #60 mesh. The drug was mixed with polymers (HPMC K100M, Ethyl cellulose, and PVP K30) in different ratios to achieve varying release profiles. Lubricants (magnesium stearate and talc) were added and mixed gently before compression.

Direct compression method

• Accurate weighing of drug and excipients 
• Passing through mesh no. 40 
• Blending in a polybag 
• Addition of lubricant and glidant 
• Compression into tablets

Table 1: Formulation design

Evaluation of Pre?compression Parameters

Flow properties and compressibility were evaluated to ensure uniform die filling and reproducible tablet weights. 

Parameters: 

• Angle of repose 

• Bulk density 

• Tapped density 

• Carr’s index 

• Hausner ratio 

Evaluation of Post?compression Parameters

Each batch was evaluated for: 

• Hardness (kg/cm²) 

• Thickness and diameter 

• Friability (%) using Roche Friabilator 

• Weight variation test 

• Drug content analysis using HPLC 

MATERIALS AND METHODS 

Medication: Bethanechol Hydrochloride

Polymers: HPMC K4M / K15M / K100M, Ethyl cellulose, NaCMC, Xanthan gum 

Excipients: Magnesium stearate, Talc, Lactose/Avicel PH 102, PVP K30 (for granulation) 

Chemicals: HCl buffer, phosphate buffer, methanol (analytical grade) 

Equipment: UV-Visible spectrophotometer, Dissolution tester (USP Type II), Hardness tester, Friabilator, Digital balance, pH meter.

In?vitro Dissolution Study

Dissolution profile were generated pH 6.8 phosphate buffer selected as media. Samples were withdrawn at predetermined intervals and analyzed at λmax of Bethanechol HCl.

Table 2: Dissolution parameter

RESULTS AND DISCUSSION

The objective of this section of the research is to evaluate the experimental data, relate the outcomes to scientific principles, and discuss the implications of the results. The study aimed to develop a formulation that ensures prolonged and controlled drug release while preserving physical stability and the desired mechanical characteristics. The findings are compared with existing literature to validate the results of the study and establish their scientific significance.

Organoleptic and Physicochemical Properties

Bethanechol Hydrochloride was observed as a white crystalline powder, lacking any odor, and possessing a slight bitterness. The compound demonstrated high solubility in water and acidic environments, moderate solubility in ethanol and methanol, and limited solubility in non-polar solvents. These characteristics validated the appropriateness of an aqueous dissolution medium for in-vitro assessment.

Solubility Studies

The solubility characteristics of Bethanechol HCl were assessed in different media to ascertain a suitable dissolution medium for the research. The findings are detailed below:

Table 3: Solubility at different pH

Bethanechol HCl exhibited good solubility in acidic and buffer media, confirming its suitability for dissolution in phosphate buffer (pH 6.8).

Pre-compression Parameters

The powder mixtures demonstrated bulk densities ranging from 0.44 to 0.47 g/mL, tapped densities from 0.51 to 0.54 g/mL, and Carr’s indices between 11% and 13%, indicating favorable compressibility.

Table 4:  Pre-compression parameter results

In-vitro Drug Release Studies

Dissolution studies were performed in a phosphate buffer (pH 6.8) for a duration of 24 hours at a temperature of 37 ± 0.5°C utilizing USP type II apparatus.

Table 5:  Dissolution profiles of formulation F1-F6

Figure 3: Dissolution profile graph of formulation F1-F6