To study the effect of various superdisintegrants and binders in the Formulation and Evaluation of Labetalol Rapid Disintegrating Tablet

Mohd Bilal Sufi; Shaikh Riyaj Khayumsab*; Rajlaxmi Deolekar

Department of Pharmaceutics, New Montfort Institute of Pharmacy, Ashti, Dist. Wardha (M.S) 442202

*Correspondence: riyaj27122000@gmail.com

DOI: https://doi.org/10.71431/IJRPAS.2026.5717            

INTRODUCTION:

Hypertension is one of the most important modifiable risk factors for cardiovascular disease (CVD), which continues to be the leading cause of global mortality and a contributor significantly share of death and disability.[1] Persistent elevation of arterial blood pressure leads to structural and functional changes in the vasculature and target organs, and is a major contributor to coronary heart disease, stroke, heart failure, and chronic kidney disease.[2] Epidemiological data indicate that hypertension affects approximately one quarter to one third of the adult population in many regions and that both prevalence and absolute numbers of affected individuals continue to rise in parallel with ageing, urbanization, and lifestyle changes.[3-7] Uncontrolled hypertension significantly increases the risk of cerebrovascular events, myocardial infarction, and progressive left ventricular hypertrophy with heart failure and contributes substantially to mortality from global CVD. [8-11] Hence, effective long‑term pharmacological management and compliance with antihypertensive therapy are necessary constituents of any strategy aimed towards lowering CVD-related morbidity and mortality. Oral solid dosage forms have remained the cornerstone of antihypertensive pharmacotherapy, as chronic treatment is required in most patients and their convenience, robustness and ease of administration play an important role in maintaining adherence and persistence with therapy

Labetalol hydrochloride is a clinically significant antihypertensive drug with combined α1-adrenergic and non-selective β-adrenergic receptor-blocking activity. Labetalol reduces blood pressure primarily by competitively antagonizing postsynaptic α1‑receptors and β1/β2‑receptors; this almost uniquely allows peripheral vascular resistance to collapse without reflex tachycardia, resulting in significant blood pressure reduction with relatively well preserved cardiac output. [15–17] It is used to primarily treat moderate or severe high blood pressure, including hypertensive emergencies, pregnancy‑induced hypertension, and situations when controlled reduction in blood pressure desired. [15-19] Labetalol is given orally as a conventional immediate‑release tablet and as parenteral formulations; the marketed oral tablets typically target twice‑ or thrice‑daily dosing in chronic therapy.[20][13] Labetalol, however, undergoes considerable first‑pass hepatic metabolism with moderate oral bioavailability and the physicochemical properties that make it an ideal candidate for non-oral routes (i.e. solubility in various acidic/alkaline media), support that careful designing of dosage forms is warranted to ensure desired in‐vivo performance. Although systemic exposure is ultimately governed by a balance of dissolution, traditional tablets, such as those manufactured with high binder content and lower porosity formulation may exhibit unpredictable disintegration and dissolution behaviour that can affect the onset of drug action, and the kinetics of dosage form disintegration. [21–23] Against this background, the formulation of rapid‑disintegrating labetalol tablets could provide an avenue to develop alternative tablet processing or formulation strategies that minimize the time to drug availability in the gastrointestinal milieu without subjecting these formulations to a presumption of improved bioavailability or more rapid clinical effect.

Rapid‑disintegrating tablets (RDTs), including fast‑dissolving or fast‑disintegrating tablets, are designed to disintegrate quickly upon contact with an aqueous medium, producing a fine dispersion of drug‑containing particles that can undergo subsequent dissolution and absorption. [17] These dosage forms aim to minimize disintegration time compared with conventional tablets, thereby reducing the lag between administration and the onset of dissolution, which is particularly relevant for drugs whose absorption rate is dissolution‑limited. including ease of administration without the need for large volumes of water, improved acceptability in patients with swallowing difficulties, and convenient use in situations where rapid disintegration is desirable. [23-25] Despite this, disintegration acts merely as a precursor towards dissolution and systemic absorption, thus RDTs must be constructed so that they can achieve a careful balance between rapid disintegration, the required mechanical strength, reasonable friability and repeatable drug release; yet still meeting pharmacopeial quality standards for immediate‑release tablets. [21, 26-28] Achieving this balance is challenging because excipients and processing conditions that promote mechanical robustness may, in some cases, hinder disintegration and water penetration.

Superdisintegrants are key components of rapidly disintegrating and immediate release tablet formulations, since these agents can provide dramatic reductions in disintegration time at relatively low levels of use. [29–31] These materials act through multiple, often overlapping mechanisms, including rapid swelling upon hydration, wicking or capillary action that transports water into the tablet matrix, general water uptake that weakens interparticulate bonds, and, in some cases, strain or deformation recovery of particles compressed during tableting. [27, 32] Commonly used synthetic superdisintegrants include crospovidone (cross‑linked polyvinylpyrrolidone), croscarmellose sodium (cross‑linked sodium carboxymethylcellulose), and sodium starch glycolate (cross‑linked carboxymethyl starch).[29–30, 33] Crospovidone is a hydrophilic material with high porosity, possessing good wicking and deformation recovery properties, allowing rapid water entry and particle dispersion through repulsion rather than swelling effect. [25, 27, 32, 34] Croscarmellose sodium exhibits a combination of swelling and wicking behaviours: it swells when hydrated to create internal stress, but water is also absorbed into its porous matrix, causing breakup of the tablet. [27, 32, 35] Numerous studies have demonstrated that both the type and concentration of superdisintegrant significantly influence disintegration time, wetting behaviour, and, indirectly, drug dissolution from immediate‑release tablets.[25, 31, 36-37] However, this is a nonlinear relationship: increasing the superdisintegrant concentration may increase disintegration up to an optimal concentration beyond which high amounts of superdisintegrant can lead to decreased porosity, gel formation or modification in microstructure that could prevent rapid disintegration or negatively influence other physical properties. [25, 27, 32, 38] Therefore, systematic evaluation of various superdisintegrants along with their concentrations in formulating a successful RDT formulation needs to be done.

Binders are equally critical excipients in tablet formulation because they promote cohesion between powder particles, improve granule or tablet integrity, and provide the mechanical strength necessary for handling, packaging, transportation, and patient use. [38] Binders are generic materials used in wet granulations as solution binders or in direct compression (as dry binders), and they comprise a wide range of ingredients such as povidone, cellulose derivatives like hydroxypropyl methylcellulose (HPMC), native and modified starches, synthetic or natural polymers [7, 33, 39–40]. Differences in binder viscosity, hydrophilicity and binding capacity significantly affect tablet hardness and tensile strength, but also friability, porosity and water penetration behaviour.[34] Use of strong or highly viscous binders tend to increase tablet hardness and decrease friability but may also decrease pore volume and limit the rate and extent of aqueous medium penetration into the tablet core, thereby prolonging disintegration and sometimes retarding dissolution.[41–42] On the other hand, less binder content leads to tablets with labile mechanical strength (low hardness), high friability, and chipping/splitting of tablets during downstream operations. As disintegration, dissolution, and mechanical robustness are interrelated quality attributes [39,7] it is important to optimize the selection of excipients in a thoughtful manner that will facilitate not only performance but manufacturability.

Binders and superdisintegrants play functionally antagonistic roles in tablets and their interaction delineates a key design space for immediate-release and rapid‑disintegrating tablets.[27, 34, 40, 43] Binders make it possible to strengthen the bonds between particles and densify the tableting structure in order to provide mechanical stability, whereas, superdisintegrants are required to weaken these same bonds when exposed to an aqueous medium through water adsorption, swelling or disruption of the matrix.[27, 32] A high binder content or use of very strong binding polymers can give tablets with too much hardness and almost no porosity, which prevents water from penetrating even after the immediate swelling effect of the super disintegrants, thus prolonging disintegration time. [41, 42] However, low-binder formulations can collapse very  rapidly but suffer from poor mechanical properties and unacceptable friability, limiting their practical utility.[39, 41] In general, for RDTs containing a drug like labetalol whose clinical efficacy is contingent on predictably low systemic exposure, balancing binder-induced mechanical strength against superdisintegrant-mediated disintegration is thus a primary formulation challenge.

Other than this, it is scientifically meaningful to compare different types of superdisintegrants and binders for the development of rapidly dissolving tablets (RDT) because type, concentration, hydration behaviour, swelling ability and binding force of binder might significantly affect tablet performance either individually or through interaction with other excipients in the formulation. [25, 27, 29-30, 36] Changes in excipient selection or level can affect fundamental quality attributes such as tablet weight variation, thickness, hardness, and friability, as well as porosity, wetting characteristics, and water‑absorption behaviour.[40–43] These attributes, in turn, modulate disintegration time and dissolution profiles, which are critical indicators of immediate‑release performance according to pharmacopoeial standards.[26, 28, 36] Several studies on fast‑disintegrating tablets of different drugs have documented that the interplay of superdisintegrant and binder markedly affects disintegration kinetics and drug‑release behaviour and that factorial or optimization designs are often required to identify formulations with acceptable combinations of rapid disintegration, mechanical integrity, and dissolution characteristics.[21, 25, 31, 36] However, the performance of a given excipient cannot be generalized across different active pharmaceutical ingredients because drug properties (such as dose, solubility, and compressibility), excipient–drug interactions, compression behaviour, and overall formulation composition strongly influence tablet microstructure and its response to aqueous media. [27, 32, 43]

The roles played by these excipients, superdisintegrants and binders, in labetalol tablet systems seem to be formulation dependent and necessitates systematic studies, especially by rapid disintegrating formulation. The work done to this point has touched upon labetalol dosage forms, including mucoadhesive buccal tablets, aimed at modulation of bioavailability of labetalol; it has also reported on the effect of type and proportion of polymers on swelling and mucoadhesion and labetalol release characteristics, with fewer reports concerning the combined effect of selected polymers and binders in a single, drug‑specific formulation platform. [11, 21] Further, the studies available for RDT have been focused almost exclusively on either optimisation of superdisintegrant or binder effects separately with focus on either taste masked or directly compressed labetalol or focused solely on disintegration or mechanical properties. [7, 25, 29, 36]  Tablet disintegration phenomena are complex and the performance of the excipients depends greatly on the drug that is being formulated; there is an obvious need to compare selected super disintegrants and binders systematically with respect to their effect on labetalol RDT systems.

In the present study, formulation of labetalol rapid disintegrating tablets and its effect of different superdisintegrant and binders on the physiochemical and performance parameters of the respective formulation has been the aim. The aim of the study is to find the best combinations of superdisintegrant and binder to achieve a suitable superdisintegrant dosage, acceptable mechanical integrity with hardness and tensile strength), acceptable overall pharmaceutical quality, and efficient drug release, with a structured formulation strategy and evaluation approach to meet the usual requirements for immediate release tablets.

MATERIALS AND METHODOLOGY

MATERIALS

Labetalol hydrochloride was procured from Swapnroop Drugs and Pharmaceuticals, Aurangabad, India. Crospovidone, sodium starch glycolate, croscarmellose sodium, mannitol, sodium saccharin, and talc were procured from Thermosil Lab Fine Chem. Polyvinylpyrrolidone (PVP K30) was obtained from Simpson, while hydroxypropyl methylcellulose (HPMC E5) and methanol were purchased from Research Lab Fine Chem Industries, Mumbai, India. Microcrystalline cellulose (MCC PH-102) and magnesium stearate were procured from Chemdyes Corporation. All chemicals, excipients, and reagents used in the study were of analytical or pharmaceutical grade and were used as received without further purification.

INSTRUMENTATION:

The study employed a Shimadzu UV-1800 UV–Visible spectrophotometer for spectrophotometric analysis and a Shimadzu TX4231 analytical balance (Mumbai) for accurate weighing of materials. Tablets were compressed using a Remik Mini Press tablet compression machine. The disintegration time of the tablets was determined using a VSI Electronics Pvt. Ltd. disintegration test apparatus, while in vitro dissolution studies were carried out using an Electro Lab TDT-08L USP Type II dissolution apparatus. Tablet hardness was measured using a Pfizer hardness tester, and friability was evaluated using a Roche friabilator manufactured by PSM Industries, Bengaluru. All instruments were calibrated prior to use in accordance with standard laboratory procedures.

METHODOLOGY:

Determination of Absorption Spectrum (λmax)

A standard stock solution of Labetalol hydrochloride was prepared by dissolving 10 mg of the drug in methanol and making the volume up to 100 mL to obtain a concentration of 100 µg/mL. The solution was then diluted further to make the concentration of 10 µg/mL. The prepared solution was scanned in the range of wavelength 200-400 nm in a UV-Visitable spectrophotometer with the background of methanol. The λmax of maximum absorbance was noted and used for all subsequent quantitative estimates such as calibrating a curve, assessing the content of drug and in-vitro dissolution studies.[45]

Preparation of Calibration Curve

Labetalol hydrochloride was dissolved in methanol to make a stock solution of 100 µg/mL. Aliquots of the stock solution were diluted with methanol to prepare final concentrations of  05, 10, 15, 20 and 25 µg/mL. The absorbance for each solution was obtained by measuring it against the blank against a UV–Visible spectrophotometer at the optimum absorbance wavelength (λmax) obtained above using methanol as the solvent. The calibration curve, which related absorbance to concentration, was plotted and the regression equation and the correlation coefficient (R²) was shown in order to ensure that the Beer-Lambert's law was followed. The calibration curve was then used in the quantitative estimation of Labetalol hydrochloride in tablet dosage forms.[46]

Fourier Transform Infrared (FTIR) Compatibility Study

FTIR spectroscopy using Attenuated Total Reflectance (ATR) technique was used to assess the drug-excipient compatibility. FTIR spectra of pure Labetalol hydrochloride and its physical mixtures with the selected excipients in a 1:1 ratio were recorded over the spectral range of 4000–400 cm⁻¹. The Absorption peaks obtained were analysed for any significant shifts in peaks such as disappearance or appearance of new peaks. The absence of chemical interaction between the drug and formulation excipients was further confirmed by the preserved characteristic frequencies in the whole functional group region which ensures their compatibility for the preparation of rapid disintegrating tablets.[47-48]

Formulation procedure of labetalol HCl tablets:

The direct compression method was used to prepare Labetalol hydrochloride rapid disintegrating tablets with the following tablet formulation as shown in Table 01. Initially, the Labetalol HCl, superdisintegrant (Crospovidone, Sodium Starch Glycolate or Croscarmellose Sodium as per batch), polymeric binder (PVP K-30 or HPMC E5 where applicable), mannitol, sodium saccharin, and microcrystalline cellulose (MCC PH-102) were accurately weighed for each formulation. The active drug, MCC PH-102, drug, mannitol, sweetener, and the selected superdisintegrant were sieved through a #60 mesh sieve to eliminate agglomerates and ensure uniform particle size. Talc and Magnesium Stearate (both passed through the #80 mesh sieve) were then added as the glidant and lubricant, respectively, and gently mixed for an additional 2–3 minutes to achieve uniform distribution and to avoid over-lubrication. The lubricated blend was assessed to the pre-compression parameters and then compressed with tablet compression machine from Remik using a Remik Mini Press to form tablets of total of 150 mg. Different compression forces were set to get uniform tablets hardness and thickness values. The compressed tablets were subjected to physical defect evaluation, sampled and kept in air tight containers for further post-compression evaluation which was carried out as per the Indian Pharmacopoeia standards.[49]

Table 01. Formulation Table for the Formulation batches (F1–F14)

Pre-compression Parameters

Angle of Repose

Angle of repose has been used to find the flowability of the powder such as the blends as per fixed funnel method. The powder mixture was enclosed in a funnel hanging in a fixed position over a flat surface, so that it flowed freely to form a heaped puddle.[50] The height, h, and radius, r, of the heap were measured and the angle of repose (θ) was computed by the use of the equation.

where h represents the height and r represents the radius of the powder cone. Lower angle of repose values indicated superior flow characteristics and suitability of the blend for direct compression.

Bulk Density

A known quantity of the powder blend was weighed, and transferred into a clean dry graduated cylinder measuring cylinder without forcing the material, and the bulk density was calculated. The volume of powder was noted when it was not used and bulk density was determined as mass of the powder per bulk volume. This parameter has been investigated to determine flow characteristics and packing properties of the powder mixes prior to compression.[51]

 Tapped Density

The tapped density of the powder blend was found by attaching the graduated cylinder to a tapped density apparatus and tapping the tube at an appropriate speed until the volume of powder did not change. The tapped volume was measured and tapped density measured as the ratio of powder mass to tapped volume. This parameter was used to give information about re-arrangement of particles and compressibility and packing efficiency of the powder blends.[51]

Carr's Compressibility Index

Carr's Compressibility Index was calculated using the experimentally determined bulk density and tapped density values according to the equation:

The compressibility index was used to evaluate the flow properties of the powder blends. Lower values indicated excellent compressibility and flow characteristics, whereas higher values suggested increased interparticle friction and relatively poor flow.[52]

Hausner's Ratio

Hausner's Ratio was calculated from the bulk density and tapped density values using the equation:

This parameter served as an additional indicator of powder flowability. A lower Hausner's ratio indicated better flow properties with minimal cohesiveness, whereas higher values suggested increased interparticle attraction and reduced flowability.[53]

Post-compression Parameters

Weight Variation

Out of each formulation batch, 20 tablets were picked up at random and each tablet was individually weighed by a calibrated digital analytic balance. Tablet weights were determined by averaging the weight of each individual tablet to find the mean weight, and also using the specifications outlined in the Pharmacopeia to calculate the percentage deviation for each tablet from the mean weight. The study was conducted to assess the uniformity of weights of the tablets and the uniformity of die filling during compression.[54]

Tablet Hardness

The crushing strength of the tablets was determined by Monsanto hardness tester. Six tablets of each formulation were selected at random and the force applied to break them in half was noted in kg/cm². Average hardness was used to assess the mechanical strength and resistance of the tablets to be broke upon handling, packing, transport and storage.[55]

Friability

Friability studies have been made in a Roche friabilator. Twenty accurately weighed tablets were put into the friabilator and rotated 100 times for 4 minutes at 25 revolutions per minute. Following the test, the tablets were de-dusted and re-weighed to determine the amount of dust removed. Weight loss during the test was used to determine the percentage friability. The friability values below 1% were classified as acceptable which corresponds to mechanical durability satisfactory.[56]

Tablet Thickness

A digital Vernier calliper was used to measure thickness of the tablets. Six tablets were randomly taken from each batch and thickness of the tablets was taken per tablet. The average thickness of the tablets was determined to evaluate the uniformity and consistency of compaction pressure exerted during tablet making.[57]

Disintegration Time

Rapid disintegrating tablets were disintegrated by USP disintegration test apparatus with the distilled water kept at 37 ± 0.5ºC as the disintegration medium and disintegration time determined. The time taken for each tablet to completely disintegrate without leaving any palpable residue was measured in seconds after the tablet was placed in the apparatus individually in each case. The incorporated super disintegrants effective as the rapid disintegration was observed.[58]

Wetting Time

To determine this the wetting time was measured by putting a round piece of paper into a dish containing 6 mL of distilled water. A tablet was gently placed on the moistened tissue paper and the time it took for water to completely absorb the tablet's surface was measured with a stopwatch. The three tests were repeated for each of the samples, and the average wetting time was determined. In general, the increased wetting time corresponds to the decreased water absorption rate, suggesting that water was absorbed more slowly and the tablet disintegrated slower.[59]

Drug Content Uniformity

Appropriate quantities of 10 tablets of each formulation were accurately weighed and finely powdered. One hundred 100 mg of Labetalol hydrochloride was added to a 100 mL volumetric flask, sonicated while dissolving in methanol and the volume was adjusted to 100 mL with methanol. The solution was passed through Whatman filter paper and proper dilutions were made in methanol. The absorbance was measured at the chosen λmax on a UV–Visible spectrophotometer. Drug content was calculated using the calibration curve and expressed as a percentage of the labelled amount.[60]

In-vitro Drug Dissolution Study

The in-vitro drug release study of the prepared RDTs was performed using USP Dissolution Apparatus Type II (Paddle Method). The phosphate buffer (pH 6.8) maintained at 37 ± 0.5ºC with a paddle rotating at 50 rpm was used to carry out the dissolution test. Ten samples of 5 mL were collected at standard time points and 30, 60, 90, 120, 240, 360, 480 and 600 seconds after placing one tablet in each dissolution vessel. Every time a sample was taken, the same amount of fresh dissolution medium was added to the sample, at the same temperature, to ensure sink conditions. The withdrawn samples were filtered through Whatman filter paper, and diluted, if needed, and then spectrophotometrically analysed at λmax chosen. A calibration curve was used to calculate the cumulative percentage drug released, and the dissolution profile of each formulation batch compared to see the effect of varying the different superdisintegrants and binders on the drug release performance. The formulation exhibiting the optimum balance of rapid disintegration, satisfactory mechanical properties, and maximum cumulative drug release was selected as the optimized formulation.[61]

 RESULT AND DISCUSSION:

 PRE-FORMULATION STUDIES:

Determination of Absorption Spectra:

The spectrum of UV absorption of the compound Labetalol hydrochloride has been obtained in methanol between the range of wavelength of 200-400 nm. The lambda max was determined at 302 nm as depicted in Fig 01.

Fig 01. Absorption spectra of Labetalol

Calibration Curve:

The calibration curves were determined by UV-visible spectrophotometer via fixed wavelength measurement. The calibration curve obtained by Beer’s Lamberts law. The calibration curve determined has R² value 0.9967 for Labetalol as depicted in Fig 02.

Fig 02. Calibration Curve for Labetalol

FTIR Compatibility Study of Labetalol with Excipients

FTIR spectra of the pure Labetalol hydrochloride and their physical mixtures with the excipients were compared for the purpose of assessing drug–excipient compatibility (Fig. 03 and 04). The characteristic functional group peaks of Labetalol hydrochloride were observed as is in the physical mixture but there were no additional peaks which could not be attributed to Labetalol hydrochloride, complete disappearance or shifting of peaks. These observations showed no interaction between the drug and the selected formulation excipients, thereby proving that all of the formulation excipients are compatible and suitable for the direct compression method to prepare rapid disintegrating tablet.

Fig. 03. FTIR of pure Labetalol

Fig. 04. FTIR of Labetalol with excipient mixture (Physical mixture 1:1)

PREFORMULATION STUDIES:

Angle of Repose:

All powder blends showed very good to good flow characteristics (angle of repose between 26.4° to 30.1°) with potability for direct compression. Formulations F11, F12 and F14 had relatively low angle of repose, indicating good flowability, based on the number of particles here, the interparticle friction is small and the orientation of the particles is good. Contrary to this, formulation F7 showed the highest angle of repose (30.1°) which means that the flow was comparatively poor but not beyond the accepted pharmacopeial limit. In general, the powder blends had acceptable flow characteristics to make sure a uniform fill during die process and uniform weight of tablets during compression.

Bulk Density:

The powder blends had bulk density values between 0.39 g/cm³ and 0.45 g/cm³, showing uniformity in packing characteristics of all the powder blends. The comparatively high bulk density of formulations with optimum concentration of powder particles packing efficiencies shown by superdisintegrants and binders highlights their function. The bulk densities were found larger for formulation F12 with a value of 0.45 g/cm³ which appeared to be better in the arrangement of the particles in its loose state before tapping, while formulation F7 had a lower bulk density of 0.39 g/cm³. All powder blends were found to be suitable for direct compression with no problems encountered, as observed.

Tapped Density:

The good packing ability after mechanical tapping is represented by the values of tapped density in the formulations from 0.48 to 0.50 g/cm³. The changes in bulk and tapped densities were small, indicating minimal rearrangement of the particles in the blends and compressibility. The formulations F11, F12 and F14 had slightly higher values of tapped density (0.50 g/cm³) which means that they have better particle consolidation while remaining formulation densities in the range of 0.48-0.49 g/cm³. The results matched the findings of uniform packing behaviour required for a good tableting compression, hence confirming the same.

Carr’s Compressibility Index:

The Carr’s Compressibility Index of all powder blends indicated the good to excellent compressibility ranging in between 10.0% and 18.8%. Formulations F12 (excellent, 10.0%) and F14 (excellent, 10.2%) possessed the lowest Carr's Index which indicated excellent compressibility and least frictional forces between the particles, whereas formulations F7 (18.8%) and F18 (19.1%) had the highest value indicating comparatively lower compressibility. However, the pharmacopoeial limits for direct compression were all held by all formulations. Optimized formulations have shown better compressibility, which may be due to more efficient packing of the particles and proper balance between the amounts of the various ingredients (binder and superdisintegrant) which help to form uniform tablets.

Table 02. Pre-compression parameters

Hausner's Ratio:

All formulation blends had good Hausner's ratio values from 1.11–1.23, which indicated good flow properties. Formulation F12 had the minimum Hausner's ratio (1.11), which meant that there was the lowest possible cohesiveness, and good powder flow while formulation F7 had the maximum value (1.23) that meant there was comparatively high friction between the particles. Although there were differences between the formulations, all had Hausner's ratio values within the acceptable range for the direct compression of powders for tablet production, indicating that the powder blends were suitable for tablet production.

Flow Character

Based on the combined evaluation of angle of repose, bulk density, tapped density, Carr's Compressibility Index, and Hausner's ratio, all fourteen powder blends exhibited satisfactory flowability and compressibility required for direct compression. Formulations with optimized levels of super disintegrants had relatively good flow properties due to better packing properties and minimized particle cohesion. Formulation F12 exhibited the most optimum flow property; this resulted in uniform fillings in the die during the process of tablet manufacture, tablet weights that were uniform from batch to batch, and similar compression characteristics in tablet manufacture from batch to batch

Post-compression parameters:

Weight variation:

The average weight of all the formulation tablets ranged at 149.88 ± 0.51 mg to 150.65 ± 0.78 mg and the weights variations shown as percentage ranged between 0.17 % and 0.42 %. All the formulations were found to meet pharmacopoeial requirement, with excellent weight uniformity and uniform die filling during compression. The optimized formulation F12 showed the minimum weight variation of 0.17%, thus the process control and powder flow during tablet manufacturing was very good.

Tablet Hardness:

The average weight of all the formulation tablets ranged at 149.88 ± 0.51 mg to 150.65 ± 0.78 mg and the weights variations shown as percentage ranged between 0.17 % and 0.42 %. All the formulations were found to meet pharmacopoeial requirement, with excellent weight uniformity and uniform die filling during compression. The optimized formulation F12 showed the minimum weight variation of 0.17%, thus the process control and powder flow during tablet manufacturing was very good.

Friability:

They were found to range from 0.35 % to 0.82 % and remain within the acceptable mechanical integrity range of formulations as per pharmacopeial standard of < 1%, reflecting excellent mechanical integrity of all the formulations. The friability value of formulation F14 was least (0.35%) and F7 was highest (0.82%). The optimized formulation F12 was found to have only 0.38% friability representing good abrasion and mechanical strength under manufacturing, packaging, transportation and handling conditions.

Tablet Thickness:

The thickness of Tablets (3.20 ± 0.01 mm to 3.30 ± 0.02 mm) indicates that there was no inconsistency in compression and die loading in all formulation batches. The minor variations recorded were not significant enough and found to be excellent dimensional uniformity. The optimized formulation F12 showed a thickness of 3.28 ± 0.03 mm, thus indicating repetitive dimension of the formulated tablets and uniform compression force.

Disintegration Time:

The disintegration time of the rapid disintegrating tablets ranged from 32 ± 1.41 seconds to 85 ± 1.41 seconds, demonstrating the significant influence of superdisintegrant type and concentration on tablet performance. The formulation with the highest disintegration time was F14 (85 seconds), followed by F13 (70 seconds) and F2 (70 seconds), and the disintegration time for the other formulations was initial times of between 32 and 36 seconds. Formulation F3 showed the shortest time of disintegration but formulation F12 showed an optimum disintegration time of 60 s, mechanical strength and was also considered to have excellent drug release as the optimized formulation.

Wetting Time:

The wetting time of the tablet was within the range of 27.67 ± 1.53 seconds to 68.00 ± 1.00 seconds showing that the medium of dissolution is spreading rapidly on the tablet matrix. The wetting time of Formulation F3 was the shortest (27.67 seconds), showed better water uptake as a result of efficient action of superdisintegrant. It was found that the longest time taken for wetting occurred with formulation F14, which means that the liquid's penetration was comparatively slower in this formulation. The optimized formulation F12 showed wetting time of 52 ± 1.00 seconds, which implies that it will give better tablet hydration with still maintaining sufficient tablet strength.

Drug Content Uniformity

The Labetalol hydrochloride content of all the formulations was found to be in between 98.2% and 99.8% indicating the uniform distribution of the drug in the tablet matrix. Each batch was found to meet the acceptance criterion set by the Pharmacopoeia and this shows good mixing efficiency when formulating. The optimized formulation F12 had maximum drug content (99.8%), which had very good content uniformity and drug formulation accuracy.

Table 03. Overall Post–compression parameters

Drug release:

The in-vitro dissolution test showed that the Labetalol hydrochloride release rate from all of RDT formulations was very rapid and progressive throughout the test indicating the superiority of direct compression method and the effect of super disintegrants on the drug release behaviour. Generally, the amount of drug released over time increased with the use of the formulations, though the release varied by superdisintegrant type, concentration, and amount of binder used with the superdisintegrant. Formulation F14 showed the least drug released (88.4%) at 600 seconds due to longer disintegration and wetting time as compared to other formulations whereas the other formulations exhibited 99.7 to 99.1% drug release respectively at the same time. Formulations with optimized level of superdisintegrants exhibited high rate of tablet hydration, water penetration rate and tablet disintegration leading to rapid drug dissolution during the first 30–120 seconds. Most drug formulations showed accelerated drug release during 240 seconds to 480 seconds, with complete tablets' disintegration, creating more surface areas for drug dissolving. The optimized formulations showed excellent dissolution efficiency with a drug release of almost 95% in 600 seconds. The increased dissolution in formulation F12 was mainly due to the concentration of superdisintegrant and the amount of binder used which contributed sufficient mechanical strength while maintaining adequate water uptake and efficient disintegration of the tablet along with prompt drug diffusion in the dissolution medium. The results indicated that the optimized formulation not only met the aim of designing a RDT but also showed its ability to achieve better dissolution performance, fast onset of drug release, and better potential for improved patient compliance.

Table 04. In–vitro drug dissolution study of the formulation batches

Fig 05. In–vitro drug dissolution study

Optimized Batch ( F12) Determination.

Among all fourteen formulations, F12 was selected as the optimized formulation based on the overall evaluation of pre-compression characteristics, post-compression quality attributes, and in-vitro drug release performance. The powder blend of F12 exhibited excellent flowability with the lowest Carr's Compressibility Index (10.0%) and Hausner's ratio (1.11), facilitating efficient direct compression. The tablets demonstrated excellent weight uniformity, satisfactory hardness (4.60 ± 0.14 kg/cm²), low friability (0.38%), acceptable thickness, and the highest drug content (99.8%). Furthermore, the formulation achieved 99.7% cumulative drug release within 600 seconds, representing the highest dissolution among all formulations while maintaining acceptable disintegration and wetting times. The balanced concentration of superdisintegrant and binder in F12 produced an optimal combination of rapid tablet disintegration, adequate mechanical strength, and maximum drug release. Therefore, formulation F12 was considered the most promising rapid disintegrating tablet formulation of Labetalol hydrochloride for improving dissolution performance and ensuring rapid therapeutic action.

CONCLUSION

Rapid disintegrating tablets of Labetalol hydrochloride were successfully formulated and evaluated by direct compression method using different disintegration aid materials (super disintegrants and binders). Excellent pre compression properties being good flowability and compressibility, were obtained for all 14 formulations. The prepared tablets met all the pharmacopoeial requirements for weight variation, hardness, friability, thickness, drug content, disintegration time and wetting time. The disintegration behaviour and drug release profile of the formulations were greatly affected by the type and concentration of superdisintegrants used in these formulations and of the binders. In the case of all batches, formulation F12 which incorporated the SADG and HPMC E5 exhibited the overall best results with excellent flow of powder, good mechanical strength, low friability, homogenous content of drug, short disintegration times, and high cumulative drug release of 99.7% within 600 s. The formulation optimized, had a desirable balance between the integrity of the tablet and a fast drug release so it can lead to improve the onset of therapeutic action and patient compliance. The overall findings suggest that, direct compression is simple and cost-effective approach for development of Labetalol hydrochloride rapid disintegrating tablets and formulation F12 can be considered as promising one for rapid disintegrating tablets of immediate release oral drug delivery system which can be improved by enhancing management of hypertension.

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