Design and Optimization of Extended-Release Mini-Tablets of Metoprolol Succinate Using Okra Stalk Powder and HPMC K100 M as Release Modifiers

Gayatri C. Pawar¹, Tanvirahmad J. Shaikh¹, Harshal D. Mahajan¹, Rajendra D. Wagh²

1.      Department of Pharmaceutics, DCS’s A. R. A. College of Pharmacy, Nagaon, Dhule.

2.      Department of Pharmaceutical Chemistry, DCS’s A. R. A. College of Pharmacy, Nagaon, Dhule.

Correspondence mail: * gayatripawar5999@gmail.com

DOI: https://doi.org/10.71431/IJRPAS.2025.4617  

INTRODUCTION:

Oral drug delivery remains the most preferred and convenient route of drug administration due to its ease of use, cost-effectiveness, and patient compliance [1,2]. However, conventional immediate-release (IR) formulations often present limitations, particularly for drugs with a short biological half-life, requiring frequent dosing [3,4]. This reduces patient compliance and can lead to fluctuations in plasma drug concentration [5]. Extended-release (ER) formulations help overcome these limitations by releasing the drug at a controlled rate [6,7].

Metoprolol Succinate, a cardioselective β1-adrenergic receptor blocker, is widely used in managing hypertension and other cardiovascular conditions [8,9]. However, its short half-life necessitates multiple daily doses [10]. Mini-tablets, due to their small size and uniformity, are promising for ER formulations [11,12].

Polymers play a key role in ER matrices [13,14]. Synthetic polymers like HPMC are effective but combining them with natural polymers like Okra stalk powder offers sustainability benefits [15-18]. Okra mucilage forms a viscous gel in aqueous environments, modulating drug release [19,20].

The study aims to develop and optimize ER mini-tablets of Metoprolol Succinate using Okra and HPMC K100 M [21].

MATERIALS AND METHODS

Materials

Metoprolol Succinate (Sun Pharmaceuticals), HPMC K100 M (Loba Chemie), MCC (Loba chemie), Magnesium Stearate & Talc (Loba Chemie), Okra stalk powder (prepared in-house).

Extraction of Okra Stalk Powder [22]

1.                  Fresh okra stalks were washed thoroughly.

2.                  Cut into small pieces and dried at 60°C.

3.                  Ground to a fine powder and sieved through a 60-mesh.

Formulation of Mini-Tablets [23,24]

Weighed drug and excipients as per 3² factorial design, mixed uniformly, lubricated, passed through 60# sieve, and compressed into mini-tablets (5 mm punch).

Evaluation Criteria

·                     Pre-compression: Bulk density, tapped density, Carr’s index, Hausner’s ratio, angle of repose.

·                     Post-compression: Weight variation, thickness, diameter, hardness, friability, drug content uniformity.

·                     In-vitro drug release: Measured at 1 hr and 12 hrs in pH 6.8 buffer.

·                     Release kinetics: Fitted to mathematical models.

Formulation Design

A 3² full factorial design was employed with 2 independent variables:

·                     X₁ – Okra stalk powder (10 mg, 15 mg, 20 mg)

·                     X₂ – HPMC K100 M (10 mg, 15 mg, 20 mg)

Dependent Variables:

·                     Y₁ – % Drug Release at 1 hour

·                     Y₂ – % Drug Release at 12 hours

Formulation Composition

Table 1: Composition of ER Mini-Tablets (Each tablet: 100 mg)

RESULTS AND DISCUSSION

Determination of λ max

The solution containing 10 ug/ml of Metoprolol Succinate in 6.8 pH phosphate buffer was prepared and scanned over 200 -800 nm against a blank using Shimadzu UV spectrophotometer 1900. The maximum wave length was observed at 221.5 nm, which was match with reported wave length.

Figure 1: UV Spectrum of Metoprolol Succinate

Drug Excipient Compatibility Study (FT-IR)

The IR spectra of a drug-polymer physical mixture was compared to that of a plain drug. Characteristic sharp distinctive peaks seen in pure drug Metoprolol Succinate, was compared with the spectra of drug and polymer mixtures. It was observed that characteristic peaks those found on pure drug spectra were still detectable in spectra of drug polymer mixture spectra, showing that the drug and polymer have no interaction. FTIR spectra of pure drug Metoprolol Succinate and drug polymer physical mixture was shown in figure 2, 3 ,4 and 5 respectively.

Figure 2: IR spectra of pure drug Metoprolol Succinate

Figure 3: IR Spectra of Okra Stalk Powder

Figure 4: IR Spectra of HPMC K 100 M

Figure 5: IR Spectra of Optimized Metoprolol Succinate Extended-Release Mini Tablets (F6)

Pre-Compression Parameters

All batches demonstrated good flowability and compressibility. Bulk density (0.621–0.667 g/cm³), Carr’s index (11.11–18.52%), Hausner’s ratio (0.844–1.158), and angle of repose (20.65–25.41°) indicated excellent to good flow. Batch F6 exhibited the best flow properties [11]. F6 showed the best flow properties.

Table 2: Pre-Compression Parameters of Powder Blends

* Indicates (N=3) ± SD

Post-Compression Parameters

Mini-tablets complied with IP limits for all parameters. Weight variation was within ±7.5%, thickness (2.3–2.7 mm), diameter (5 mm), hardness (6.8–7.7 kg/cm²), friability (<0.5%), and drug content uniformity (97.2–99.5%). Batch F6 showed superior hardness, minimal friability, and optimal content uniformity. All mini-tablets met pharmacopeial standards. Batch F6 exhibited superior hardness and uniform drug content [12].

Table 3: Physical Parameters of Mini-Tablets

All batches passed IP limits for weight variation, friability (<1%), and drug content uniformity.

Factorial Design Optimization

Pre-compression and post-compression parameters were assessed as per standard methods [25-27]. In-vitro drug release was studied and release kinetics were analyzed [28,29].

Table 4: Factorial Design Response Table

Figure 6: Surface Plot of Drug Release at 1 Hour

Figure 7: Contour Plot of % Drug Release at 12 Hours

Drug Release and Kinetics

In-vitro drug release studies were conducted for all nine formulations (F1–F9) over 12 hours in pH 6.8 buffer. The percentage drug release at 1 hour (Y₁) and 12 hours (Y₂) was determined for each batch. Higher concentrations of Okra and HPMC slowed initial release and sustained the drug over 12 hours. Batch F6 (20 mg Okra + 15 mg HPMC) showed the best profile with 27.4% release at 1 hr and 99.1% at 12 hr.[23,24].

Table 5: In-Vitro Drug Release Profile at 1 hr and 12 hr

Figure 8: Comparison of % Drug Release at 1hr and at 12hr from Metoprolol Succinate ER Tablets.

A graph of drug release vs. time for F6 demonstrated a controlled release pattern. Drug release data were fitted to kinetic models. F6 best fit the Korsmeyer–Peppas model (R²=0.994) with n=0.68, suggesting anomalous (non-Fickian) diffusion. The Higuchi model also fit well (R²=0.987), confirming diffusion-controlled release.

Table 6: Kinetic Model Fitting of Optimized Batch F6

Batch F6 showed sustained drug release with minimal burst effect and followed anomalous diffusion kinetics.

CONCLUSION

The study successfully developed ER mini-tablets of Metoprolol Succinate using Okra stalk powder and HPMC K100 M. Batch F6 was optimized with balanced initial and extended release. The results demonstrate that Okra stalk powder is a sustainable, biocompatible alternative to synthetic polymers in ER formulations.

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