Formulation Optimization and Evaluation of Orodispersible Tablet of Valsartan by using Co-Processed Super Disintegrants

Orodispersible Tablet

Orodispersible tablets (ODTs), commonly referred to as fast dissolving tablets or orally disintegrating tablets, are advanced solid dosage forms engineered to breakdown and dissolve rapidly in saliva without the necessity of water.  These tablets are a practical option for pediatric, geriatric, and dysphagic those who have trouble swallowing conventional pills or capsules. ODTs are gaining popularity in pharmaceutical research because of their simplicity of administration, increased patient compliance, and potential for speedier start of effect. ODTs are created by combining superdisintegrants, flavor masking chemicals, and innovative production procedures such direct compression, freeze drying (lyophilization), and sublimation.  These approaches guarantee that the active pharmaceutical ingredient (API) disintegrates quickly after being placed in the mouth, allowing for absorption.  ODTs are particularly useful for medications that undergo first-pass metabolism or require immediate therapeutic effect, making them suitable for allergies, pain, nausea, and neurological problems.  With the growing demand for patient-centric dosage forms, ODTs have emerged as a viable drug delivery platform. 

2. Hypertension

Medications used to treat high blood pressure are known as antihypertensive medications. Therefore, it is essential to effectively treat hypertension in order to prevent serious consequences and lower morbidity and mortality.  Medications used to treat high blood pressure are known as antihypertensive medications. These comprise a number of types, including Angiotensin II receptor blockers (ARBs), ACE inhibitors, beta-blockers, calcium channel blockers and diuretics.  The severity of the ailment, co-morbidities, patient compliance, and possible adverse effects all influence the therapeutic selection.

  3.Valsartan

Angiotensin II receptor blockers, or ARBs, like valsartan, are frequently used to treat heart failure, hypertension, and myocardial infarction.  It reduces vasoconstriction and aldosterone production by specifically blocking angiotensin II's binding to the AT1 receptor in a variety of tissues, including the adrenal gland and vascular smooth muscle.  As a result, blood pressure drops and the heart has less work to do.In the Biopharmaceutical Classification System (BCS), the medication is classified as Class II, indicating poor solubility but significant permeability.  This has sparked a lot of interest in pharmaceutical research aimed at increasing its bioavailability using different formulation strategies.

Table 1: Composition of Valsartan Oro –Dispersible Tablet

    Evaluation of Oro dispersible tablet

Physical Appearance

A patient's acceptance of an orodispersible tablet depends on its entire look, which includes its visual identity, color presence or absence, size and form, surface texture, consistency, and overall elegance.

Friability

The Roche Friabilat or was used to assess friability in order to determine the tablet's strength. Ten undusted tablets were weighed, put through 100 cycles of friability, undusted, and then weighed one again. The following formula was then used to get the % friability. Friability of less than 1% is regarded as acceptable.

 Percentage friability = (Initial weight-Final weight) / Initial weight ×100

Hardness

A crucial factor in preventing tablet breaking during handling, storage, and transit is the tablet's hardness.  Using the Monsanto hardness tester, the tablets' hardness was measured and recorded in kg/cm2.

Weight variation test

Twenty tablets were chosen at random from each batch and weighed separately for weight variation of tablet studies. The average weight and standard deviation of twenty tablets were then computed.

Drug content uniformity

Twenty pills were selected at random, weighed, and ground into powder.  After precisely weighing the powder equal to 100 mg of the medication, it was dissolved in 100 milliliters of phosphate buffer 6.8.  The mixture was given a good shake.  Filtration with Whatman filter paper 41 eliminated the undissolved particles.  After the dilutions were created, the diluted solutions' absorbance was measured at 248 nm.

Disintegration time

All formulations' disintegration times were ascertained using the tablet disintegration device.  Each of the six distilled water tubes contained one pill.  The temperature was maintained at 37± 2°C, and the amount of time it took for the pill to dissolve fully was noted.

In – vitro drug release

USP apparatus-II (paddle) was used for the in-vitro drug release, which involved rotating the paddle at 50 rpm and 37±0.5°C with 900 cc of 6.8 pH phosphate buffer.  Fresh medium of 6.8 pH phosphate buffer was used in place of 1 ml of the sample, which was removed at prearranged intervals.  After passing through Whatman filter paper and being appropriately diluted, the samples were examined at 223 nm.

RESULT AND DISCUSSION

Preformulation studies

Identification of drug

FTIR Spectroscopy

The FT-IR spectra of the pure medication  valsartan  is presented in the figure. 6.1. The principal absorption peaks of valsartan were observed at 1500 – 1750 cm -1(C=O), 2210 - 2260 cm-1(C-N) and 2000 - 2500 cm-1 (CH3bond).

Figure 1: FTIR spectra of valsartan

Figure 2 :  FTIR spectra of Crospovidone

Figure 3: FTIR spectra of Guar gum

Figure 4:  FTIR sectra of Microcrystalline

Figure 5: FTIR spectra of Magnesium stearate

Figure 6:  FTIR spectra of Talc

Figure 7:  FTIR spectra of Mannitol

DSC of Valsartan

From DSC thermograms, melting point of valsartan was found to be 117°C which was reported in literature and procured drugs in pure form. Endothermic peak of pure drug valsartan was shown to be 108.42°C.

Figure 8: DSC thermogram of mixture

Melting point

The capillary technique was used to determine Valsartan's melting point.  The melting point of valsartan was 116°C, and it reached its full melting point at 117°C.

Solubility

Table 2: Results of solubility studies of Valsartan in various solvents

Partition co-efficient

The partition coefficient (log P) of valsartan in an octanol-water system was 1.499, indicating that the drug had moderate lipophilicity. A log P value around 1 suggested that valsartan had a balanced distribution between the hydrophobic (octanol) and hydrophilic (water) phases. This moderate lipophilicity suggested that valsartan could pass through biological membranes, which are typically lipid-based, while also being sufficiently soluble in aqueous environments to allow for absorption in the body. The log P value of 1.499 suggested that valsartan likely exhibited favorable pharmacokinetic properties, such as good oral bioavailability, as it could efficiently partition between the aqueous and lipid phases. However, its moderate lipophilicity also implied that careful formulation strategies might have been needed to optimize its solubility and absorption in different environments within the body.

Drug excipients compatibility studies

No interaction of Valsartan utilizing excipients was found in FTIR of physical mixture (1:1). The Valsartan peaks remained unchanged and were identified as 3419 cm?¹ for N-H stretch, 2949cm?¹ for C-H stretch, 1749 cm?¹ for Carboxylic stretch, 1600cm?¹ for C=O bend, 1105cm?¹ for C-N bond.

Figure 9: FTIR spectra of Physical mixture

Precompression study

Pre-compression parameter evaluation is essential for determining the cohesiveness, flowability, and compressibility of powder blends utilized in orodispersible valsartan tablet formulations.  The finished pills' homogeneity and quality are greatly impacted by these characteristics.  The appropriateness of each formulation (F1–F9) for direct compression was assessed using parameters such bulk density, tapped density, Carr's index, Hausner's ratio, and angle of repose.

Bulk density

Bulk density (0.472–0.484 g/cm³) showed minimal variation across F1–F9, with F1 exhibiting the highest and F9 the lowest values. This indicates uniform packing properties and acceptable flow behavior among all formulations, suggesting suitability for direct compression.

Tapped Density:

Tapped density values for formulations F1 to F9 ranged between 0.570 and 0.582 g/cm³. Formulations F1, F4, and F6 exhibited comparatively higher values, suggesting enhanced packing potential. A higher tapped density generally reflects better compressibility, which is favorable for tablet formation. However, for orodispersible tablets, achieving an optimal tapped density is essential to ensure both adequate mechanical strength and rapid disintegration.

Angle of Repose:

The range of the angle of repose was 30.12° to 39.23°, indicating variation in flow properties among the formulations. F9 showed the lowest angle, suggesting excellent flow, while F1 exhibited the highest, indicating relatively poor flowability. Formulations F7, F8, and F9 demonstrated better flow behavior, which is critical for uniform die filling and consistent tablet weight. Improved flow properties contribute to efficient tablet manufacturing and minimize the risk of weight variation and mechanical defects.

Carr’s Index:

Carr’s index for all formulations ranged from 16.0 to 18.9%. F4 exhibited the highest value (18.9%), indicating lower flowability and higher compressibility. Formulations F1, F2, and F3, with values below 18%, demonstrated relatively better flow. As values under 20% generally suggest acceptable flow, most formulations were within suitable limits, though F4 may require optimization to enhance flow characteristics.

Hausner’s Ratio:

Hausner’s ratio, an important indicator of powder flowability, was observed to range between 1.19 and 1.233 across all formulations. Lower values (as seen in F7 and F9) are associated with better flow characteristics, which facilitate uniform die filling and consistent tablet weight. In contrast, F4 demonstrated the highest ratio (1.233), suggesting relatively poor flow. Although all formulations remained within the acceptable limit of <1.25, the elevated value in F4 indicates potential difficulties in achieving consistent tablet formation and may warrant formulation optimization to enhance flow behavior.

Table 3: Results of pre-compression parameters

Thickness Evaluation

ODTs were between 2.93 ± 0.01 mm and 3.01 ± 0.03 mm thickness, falling within the acceptable limit of 2.5–3.5 mm for oro-dispersible tablets. All formulations (F1–F9) showed minimal variation, indicating uniformity. This optimal thickness ensures adequate mechanical strength, ease of packaging, and patient compliance.

Friability Study

The friability of the tablet formulations ranged from 0.56 ± 0.02 to 0.81 ± 0.02. The lowest friability was noted in F8 (0.56 ± 0.02), indicating excellent mechanical strength, whereas F3 (0.81 ± 0.02) showed the highest friability, suggesting a comparatively higher tendency to breakage. All formulations exhibited friability values within acceptable limits (NMT 1%), confirming their robustness during handling. Among these, F6, F1, and F7 demonstrated better resistance to abrasion, indicating superior durability.

Weight Variation:

Tablet weights ranged from 98.64 ± 0.26 to 100.52 ± 0.25 mg, within the acceptable ±5% limit. All formulations showed consistent weight, indicating uniform drug content.

Hardness

Tablet hardness ranged from 2.15 ± 0.02 to 2.75 ± 0.02 kg, indicating acceptable mechanical strength across all formulations. F5 exhibited the highest hardness (2.75 ± 0.02 kg), suggesting greater resistance to breakage, while F1 had the lowest (2.15 ± 0.02 kg), making it more prone to damage. Formulations F3, F6, and F7 showed balanced hardness, ensuring sufficient robustness along with proper disintegration characteristics.

Drug content uniformity

All formulations demonstrated good drug content uniformity, ranging from 96.32 ± 0.03% (F6) to 99.96 ± 0.03% (F3), ensuring each tablet contains the correct amount of valsartan for consistent therapeutic efficacy. Notably, formulations F2, F3, and F8 showed values close to 99%, which is ideal for uniform dosing. Overall, the results confirm excellent drug content uniformity across all formulations, supporting reliable and consistent therapeutic outcomes.

Disintegration time

Disintegration time ranged from 14.22 ± 0.05 to 56.32 ± 0.02 seconds. F3 showed the fastest disintegration (14.22 ± 0.05 s), indicating rapid dissolution suitable for ODTs. F5 (54.91 ± 0.07 s) and F6 (56.32 ± 0.02 s) had slower disintegration, which is not ideal for ODTs. Formulations F2 (22.18 ± 0.02 s), F8 (26.44 ± 0.04 s), and F4 (32.41 ± 0.02 s) exhibited moderate disintegration times aligning with typical ODT criteria. Thus, F3 is the most promising formulation, while F5 and F6 require optimization to improve disintegration.

Table 5: Result of evalution of Valsartan Oro- dispersible tablet

Among the formulations, F3 (2% crospovidone, 10% guar gum) showed the fastest and most complete drug release, reaching nearly 99.5% at 30 minutes with a rapid initial release of 78%. Formulations with higher guar gum content like F8 (3.5% crospovidone, 11% guar gum) provided a slower but steady release, ideal for sustained action. Lower guar gum levels, as in F4 and F5, generally resulted in moderate to slower release profiles, while very high crospovidone and guar gum levels in F6 led to the slowest release, likely due to excessive gelling. Overall, the balance between crospovidone and guar gum critically influences the drug release rate, with moderate crospovidone and higher guar gum concentrations favoring rapid and near-complete valsartan release.

Figure10:  Drug release of F1 , F2 ,F3 and F4 formulation

Drug release of F5, F6, F7, F8 and F9 formulation