1Shiva Trusts, Shivajirao Pawar College of Pharmacy, Pachegaon, Newasa, Ahilyanagar, Maharashtra-413725, India.
2,3,4Dinesh Bambade College of Pharmacy & Research, Mahalangra Village Tq. Chakur Dist. Latur, Maharashtra-413512, India.
5,6Somayya Diploma in Pharmacy College, Akashwani Rd, Wadgaon, Chandrapur, Maharashtra-442401
7,8Ashoka Institute of Pharmacy, Chandrapur.
Salbutamol sulphate, a short-acting ??-adrenergic receptor agonist, is widely prescribed for the management of asthma and chronic obstructive pulmonary disease (COPD). Its higher selectivity for ??-receptors over ??-receptors ensures targeted pulmonary activity with reduced cardiac side effects. In the present study, mouth dissolving tablets (MDTs) of salbutamol sulphate were developed using the direct compression method with different concentrations of super disintegrants, including croscarmellose sodium, sodium starch glycolate, and crospovidone. The prepared formulations were assessed for pre- and post-compression characteristics such as hardness, friability, weight variation, drug content uniformity, disintegration time, water absorption ratio, wetting time, and in vitro dissolution. All formulations exhibited acceptable weight variation (within ±7.5%), hardness between 3.4–4.0 kg/cm², and friability values below 1%. Disintegration times were found to be less than one minute, while drug content ranged from 98.5% to 101%. Wetting time was recorded at around 8 seconds, with a water absorption ratio of 89.84%. Among all formulations, DC6 containing 7.5% crospovidone demonstrated the most promising results, with a rapid disintegration time of 27 seconds and an in vitro drug release of 98.45% within 18 minutes. These findings confirm that crospovidone is highly effective in producing fast-dissolving salbutamol tablets suitable for rapid onset of action in respiratory conditions.
Among the various routes of drug administration, the oral route continues to be the most preferred owing to its safety, convenience, and cost-effectiveness, which ultimately enhances patient compliance [1]. Oral drug delivery is widely utilized; however, several limitations are associated with it. These include poor solubility of certain drugs, degradation in the acidic gastric environment, enzymatic metabolism, gastrointestinal (GI) irritation, food–drug interactions, and variability in gastric emptying time [2]. Additionally, a considerable number of patients, particularly pediatrics, geriatrics, and those with dysphagia, often face difficulty in swallowing conventional tablets and capsules, leading to poor adherence and compromised therapeutic outcomes [3]. To overcome these challenges, Mouth Dissolving Tablets (MDTs) have emerged as a promising alternative dosage form. These tablets are designed to disintegrate or dissolve rapidly in the oral cavity without the need for water, releasing the active drug for immediate absorption, thereby offering a faster onset of action [4]. MDTs also provide patient-friendly administration, especially for populations that have difficulty swallowing solid dosage forms. For a drug to be suitable for formulating into MDTs, certain criteria must be fulfilled. The drug should possess a low to moderate dose, good stability in saliva, partial non-ionization in the oral cavity, and adequate permeability across the oral mucosa. Moreover, small to moderate molecular weight and acceptable taste are essential prerequisites, as bitterness or unpleasant odor may hinder patient acceptability [5]. An ideal MDT should disintegrate within seconds in the mouth, provide a pleasant mouthfeel, be compatible with taste-masking strategies, and leave minimal or no residue after administration. Additionally, MDTs should demonstrate robustness against environmental factors such as humidity and temperature, while being feasible for large-scale production using conventional manufacturing techniques at reasonable cost [6]. The advantages of MDTs include ease of administration without water, improved patient compliance in pediatrics, geriatrics, and psychiatric patients, convenience during travel, and rapid drug dissolution leading to faster therapeutic action. Despite these advantages, certain limitations exist drugs requiring high doses are difficult to formulate into MDTs, and patients with reduced saliva production (e.g., Sjögren’s syndrome) may not benefit optimally from this dosage form [6]. Considering these aspects, Salbutamol Sulphate, a β2-adrenergic receptor agonist widely used for the management of asthma and chronic obstructive pulmonary disease (COPD), presents as a suitable candidate for MDT formulation. Its rapid onset of action is highly desirable in emergency conditions such as acute asthmatic attacks, where immediate relief is critical. Thus, formulating Salbutamol Sulphate into a mouth dissolving tablet can potentially enhance patient compliance, improve onset of therapeutic action, and provide a convenient dosage form for populations requiring quick relief.
Figure 1: Salbutamol Sulphate
MATERIALS AND METHOD:
MATERIALS:
Salbutamol sulphate was obtained as a gift sample from FDC Ltd., Aurangabad, India. Superdisintegrants such as Croscarmellose sodium were procured from S.D. Fine Chemicals Ltd., Mumbai, Crospovidone from Cipla Ltd., Central Mumbai, and Sodium starch glycolate from Maple Biotech Pvt. Ltd., Pune. All other chemicals and reagents used in the study were of analytical grade and utilized without further purification.
Formulation of Mouth Dissolving Tablets of Salbutamol Sulphate
The mouth dissolving tablets (MDTs) of Salbutamol sulphate were prepared using the direct compression technique [7]. Initially, all the ingredients were passed through a #60 mesh sieve to ensure uniform particle size. The weighed quantity of Salbutamol sulphate was blended with diluents such as lactose and microcrystalline cellulose using a mortar and pestle to achieve homogeneity. Superdisintegrants, namely croscarmellose sodium, sodium starch glycolate, and crospovidone, were then incorporated into the blend. Finally, magnesium stearate and talc were added as lubricants to complete the mixture. The prepared powder blend was evaluated for pre-compression parameters and subsequently compressed into tablets using a 10-station rotary tablet compression machine (Rimek, India) fitted with 7 mm flat-faced punches.
Table 1: Formulation of salbutamol sulphate mouth dissolving tablets prepared by direct compression method
|
Sr. No |
Ingredients |
DC1 |
DC2 |
DC3 |
DC4 |
DC5 |
DC6 |
|
1. |
Salbutamol sulphate.(mg). |
2.00 |
2.00 |
2.00 |
2.00 |
2.00 |
2.00 |
|
2. |
Lactose (mg). |
69.00 |
67.00 |
69.00 |
67.0 |
69.00 |
67.0 |
|
3. |
Microcrystalline cellulose. |
20.00 |
20.00 |
20.00 |
20.0 |
20.00 |
20.0 |
|
4. |
Crospovidone (%). |
-- |
-- |
-- |
-- |
3.00 |
5.00 |
|
5. |
Crosscarmellose sodium(%). |
3.00 |
5.00 |
-- |
-- |
-- |
-- |
|
6. |
Sodium starch glycolate(%) |
-- |
-- |
3.00 |
5.00 |
-- |
-- |
|
7. |
Magnesium stearate (mg). |
2.00 |
2.00 |
2.00 |
2.00 |
2.00 |
2.00 |
|
8. |
Talc (mg). |
4.00 |
4.00 |
4.00 |
4.00 |
4.00 |
4.00 |
|
9. |
Total weight (mg). |
100 |
100 |
100 |
100 |
100 |
100 |
Table 2: Formulation of salbutamol sulphate mouth dissolving tablets prepared by direct compression method (50-Tablet)
|
Sr. No. |
Ingredients |
Dc1 |
DC2 |
DC3 |
DC4 |
DC5 |
DC6 |
|
1 |
Salbutamol sulphate(mg). |
100 |
100 |
100 |
100 |
100 |
100 |
|
2 |
Lactose(mg). |
3450 |
3350 |
3450 |
3350 |
3450 |
3350 |
|
3 |
Microcrystalline cellulose(mg) |
1000 |
1000 |
1000 |
1000 |
1000 |
1000 |
|
4 |
Crospovidone (%) |
-- |
-- |
-- |
-- |
150 |
250 |
|
5 |
Crosscarmellose sodium (%) |
150 |
250 |
-- |
-- |
-- |
-- |
|
6 |
Sodium starch glycolate (%) |
-- |
-- |
150 |
250 |
-- |
-- |
|
7 |
Magnesium stearate. (mg) |
100 |
100 |
100 |
100 |
100 |
100 |
|
8 |
Talc. (mg) |
200 |
200 |
200 |
200 |
200 |
200 |
|
|
Total weight (mg) |
5000 |
5000 |
5000 |
5000 |
5000 |
5000 |
Evaluation of mouth dissolving tablets
The prepared mouth dissolving tablets (MDTs) of Salbutamol sulphate were subjected to a series of evaluation tests to ensure their quality, performance, and compliance with pharmacopeial standards.
Hardness Test
The mechanical strength of the tablets was evaluated using a hardness tester, and the results were expressed in kg/cm². For each formulation, three tablets were randomly selected, and the mean hardness along with standard deviation was calculated to assess uniformity in tablet strength [8].
Friability Test
Friability testing was performed to determine the ability of tablets to resist abrasion and breakage during handling. Twenty tablets from each batch were initially weighed (W_initial) and then placed in a Roche friabilator, which was operated at 25 rpm for 4 minutes (equivalent to 100 revolutions). The tablets were reweighed after the test (W_final), and the percentage weight loss was calculated. A friability value of less than 1% was considered acceptable [8].
Drug Content Uniformity
The uniform distribution of Salbutamol sulphate within the tablets was determined by drug content analysis. Five tablets were accurately weighed, powdered, and an amount equivalent to 100 mg of drug was transferred into 100 ml of phosphate buffer (pH 6.8) to obtain a concentration of 1000 µg/ml. From this stock solution, 15 ml was withdrawn and diluted to 100 ml with phosphate buffer, resulting in a 150 µg/ml solution. The absorbance of this solution was measured at 277 nm using a UV-Visible spectrophotometer, and the drug content was calculated against a standard calibration curve [8].
Water Absorption Ratio
The water absorption capacity of the tablets was evaluated to predict their wetting efficiency. The initial weight of a dry tablet (W_b) was noted, after which it was placed in a petri dish containing distilled water until completely wetted. The tablet was then reweighed (W_a), and the water absorption ratio (R) was calculated using the following formula:
R=(Wa−Wb)Wa×100
This parameter is crucial as it directly influences the disintegration and dissolution behavior of MDTs [9].
In-Vitro Disintegration Test
The disintegration time of the tablets was evaluated using the USP disintegration apparatus without a disk. Six tablets from each formulation were placed in 900 ml of distilled water maintained at 37 ± 0.5 °C. The time taken for each tablet to completely break down into fine particles without leaving any residue was recorded in seconds. A shorter disintegration time is a desired property of MDTs [9].
In-Vitro Drug Release Studies
The dissolution profile of the formulated tablets was studied using a USP type I dissolution apparatus (basket type, Electrolab, India). The dissolution medium consisted of 900 ml of phosphate buffer (pH 6.8), maintained at 37 ± 0.5 °C with the basket rotation set at 50 rpm. At predetermined time intervals of 3 minutes, 5 ml of the sample was withdrawn and replaced with an equal volume of fresh medium to maintain sink conditions. The collected samples were suitably diluted with phosphate buffer and analyzed spectrophotometrically at 277 nm to determine the cumulative percentage of drug release [9].
RESULT AND DISCUSSION
Preformulation Studies:
Salbutamol sulphate mouth dissolving tablets so prepared were evaluated for various parameters like weight variation, hardness, friability in-vitro disintegration, drug polymer interaction, drug content uniformity, water absorption ratio, wetting time, in vitro drug release. The melting point of salbutamol sulphate was determined by using capillary method and it was found to be 157°C. This value is within range of 157-1580C. According to result shown in table no13.Each tablet of every batch was weighed, the percentage deviation was less than ±7.5% indicating that tablets are uniform in weight.
Pre-compression Parameters of Powder Blend
The prepared powder blends of Salbutamol sulphate formulations (DC1–DC6) were evaluated for pre-compression characteristics including bulk density, tapped density, angle of repose, Carr’s index, and Hausner’s ratio.
Table 3: Results of Pre-compression parameters of powder
|
FC |
Bulk density |
Tapped density |
Angle of repose |
Carr’s index |
Hausner’s ratio |
|
DC1 |
0.490 |
0.372 |
25.030 |
12.75 |
0.98 |
|
DC2 |
0.436 |
0.413 |
25.930 |
11.60 |
0.88 |
|
DC3 |
0.445 |
0.441 |
24.665 |
12.07 |
0.92 |
|
DC4 |
0.498 |
0.501 |
26.832 |
13.83 |
1.06 |
|
DC5 |
0.590 |
0.362 |
25.340 |
12.75 |
1.02 |
|
DC6 |
0.474 |
0.489 |
25.661 |
11.51 |
0.97 |
The bulk density of the formulations ranged between 0.436 and 0.590 g/cm³, while the tapped density was between 0.362 and 0.501 g/cm³, indicating good packing properties of the powder blends. The angle of repose for all formulations was found in the range of 24.665° to 26.832°, which falls within the acceptable limits (<30°), suggesting good flow characteristics. The Carr’s index values ranged from 11.51% to 13.83%, while the Hausner’s ratio varied between 0.88 and 1.06. Both parameters confirmed good compressibility and flowability of the blends, which are essential for uniform die filling and consistent tablet weight. Overall, the pre-compression parameters indicated that the powder blends possessed suitable flow and packing properties, making them appropriate for direct compression technique.
Post-compression Parameters of Tablets
The compressed tablets were evaluated for hardness, friability, thickness, drug content uniformity, weight variation, and disintegration time.
Table 4: Results of post-compression parameters
|
FC |
Hardness (Kg/cm2) |
%Friability |
Thickness (mm) |
Drug content |
Weight variation |
Disintegration time (sec) |
|
DC1 |
3.5 |
0.84 |
3.2 |
98.5 |
99.6 |
29 |
|
DC2 |
3.8 |
0.76 |
2.9 |
98.8 |
98.9 |
35 |
|
DC3 |
3.4 |
0.64 |
2.9 |
98.50 |
99.4 |
38 |
|
DC4 |
4.0 |
0.72 |
3.5 |
98.20 |
99.8 |
40 |
|
DC5 |
3.6 |
0.56 |
3.3 |
99.80 |
98.8 |
32 |
|
DC6 |
3.5 |
0.82 |
2.9 |
100.00 |
99.6 |
27 |
The hardness of the tablets was observed between 3.4 and 4.0 kg/cm², which were within the acceptable range, ensuring adequate mechanical strength while maintaining fast disintegration. The friability values were found between 0.56% and 0.84%, all below the pharmacopeial limit of 1%, indicating good resistance to mechanical stress during handling and transportation. The thickness of the tablets ranged between 2.9 and 3.5 mm, showing minimal variation and confirming uniform compression. The drug content uniformity of all formulations was within 98.2% to 100%, which lies well within the acceptable pharmacopeial limits (±5%), ensuring dose accuracy. The weight variation results (98.8%–99.8%) were consistent, further supporting uniformity of the tablet mass. The disintegration time ranged from 27 to 40 seconds, with DC6 showing the fastest disintegration (27 sec), followed closely by DC1 (29 sec), while DC4 exhibited the longest time (40 sec). All formulations complied with the pharmacopeial requirement for mouth dissolving tablets (<60 sec). Overall, the post-compression evaluation confirmed that the formulated MDTs of Salbutamol sulphate exhibited desirable mechanical strength, excellent friability resistance, uniformity in weight and drug content, and rapid disintegration, making them suitable for fast therapeutic action in patients requiring immediate relief.
In-Vitro Dissolution Studies
The in-vitro dissolution profiles of Salbutamol sulphate mouth dissolving tablets were evaluated in phosphate buffer pH 6.8, and the cumulative percentage drug release was recorded at predetermined time intervals for formulations DC1–DC6. Formulations DC1 and DC2 exhibited a rapid onset of drug release, with more than 45% of drug released within the first 3 minutes. DC2 demonstrated a comparatively faster dissolution profile than DC1 at all sampling points. At 12 minutes, DC2 showed 87.45% release, whereas DC1 released only 75.25%. By the end of 18 minutes, DC2 achieved nearly complete release of 95.28%, while DC1 reached 88.34%. This difference suggests that the superdisintegrant concentration or type used in DC2 enhanced tablet disintegration and facilitated faster drug dissolution compared to DC1.
Table 5: Dissolution data of salbutamol sulphate in phosphate buffer pH 6.8 from Tablets of DC1-DC2
|
Time (min) |
DC1 (%) |
DC2 (%) |
|
0 |
0 |
0 |
|
3 |
47.63 |
49.35 |
|
6 |
59.95 |
63.40 |
|
9 |
69.96 |
75.90 |
|
12 |
75.25 |
87.45 |
|
15 |
82.76 |
91.10 |
|
18 |
88.34 |
95.28 |
Figure 2: In- vitro release of salbutamol sulphate from tablets of DC1-DC2
Both DC3 and DC4 displayed moderate drug release compared to DC1 and DC2. At 3 minutes, DC3 released 45.88% of the drug, while DC4 released 49.35%, indicating a slightly better performance of DC4 in the early phase. Over the entire dissolution period, DC4 consistently showed higher release values than DC3. At 18 minutes, DC4 achieved 89.56% release, compared to 87.18% from DC3. This trend suggests that formulation DC4 had better disintegration and dissolution characteristics, though neither reached the extent of release obtained with DC2.
Table 6: Dissolution data of salbutamol sulphate in phosphate buffer pH 6.8 from tablets of DC3-DC4
|
Time (min) |
DC3 (%) |
DC4 (%) |
|
0 |
0 |
0 |
|
3 |
45.88 |
49.35 |
|
6 |
58.56 |
62.45 |
|
9 |
68.89 |
72.30 |
|
12 |
73.98 |
78.23 |
|
15 |
80.54 |
84.88 |
|
18 |
87.18 |
89.56 |
Figure 3: In-vitro release of salbutamol sulphate from tablets ofDC3-DC4
Formulations DC5 and DC6 showed the most promising dissolution behavior among all formulations. Within 3 minutes, more than 50% of the drug was released, indicating very rapid onset of dissolution. Both formulations continued to release drug efficiently, with DC6 showing slightly faster performance than DC5 at every time point. By 12 minutes, DC6 reached 89.72% release, while DC5 showed 88.54%. At 18 minutes, DC6 achieved almost complete drug release of 98.45%, whereas DC5 released 96.51%. This indicates that DC6 had the most optimized composition for rapid disintegration and dissolution, likely due to an effective superdisintegrant ratio and excipient synergy.
Table 7: Dissolution data of salbutamol sulphate in phosphate buffer pH 6.8 from tablets of DC5-DC6.
|
Time (min) |
DC5 (%) |
DC6 (%) |
|
0 |
0 |
0 |
|
3 |
50.16 |
52.34 |
|
6 |
64.18 |
65.35 |
|
9 |
75.64 |
76.80 |
|
12 |
88.54 |
89.72 |
|
15 |
93.73 |
94.20 |
|
18 |
96.51 |
98.45 |
Figure 4: In-vitro release of salbutamol sulphate from tablets of DC5-DC6
Across all formulations, drug release was rapid, confirming the efficiency of the mouth dissolving tablet design. However, significant differences were observed in the extent and rate of release. Formulations DC5 and DC6 exhibited superior dissolution profiles, achieving more than 95% release within 18 minutes, which is desirable for achieving a fast therapeutic response in acute asthma management. DC2 also performed well, with 95.28% release at 18 minutes, outperforming DC1, DC3, and DC4. Overall, DC6 demonstrated the best dissolution profile, releasing 98.45% of Salbutamol sulphate within 18 minutes, followed by DC5 and DC2. These results suggest that DC6 is the most promising formulation for developing an effective and patient-compliant mouth dissolving tablet of Salbutamol sulphate.
CONCLUSION
The present research successfully developed mouth dissolving tablets of salbutamol sulphate using direct compression with different superdisintegrants. The prepared tablets were found to be of uniform weight, with no signs of chipping or capping, and demonstrated adequate hardness (3.4–4.0 kg/cm²) and friability below 1%. Compatibility studies confirmed that the drug was stable with the selected excipients. Among all formulations, DC6 containing crospovidone at 7.5% exhibited the most desirable properties, including a rapid disintegration time of 27 seconds, a wetting time of 8 seconds, and an excellent water absorption ratio of 89.84%. Furthermore, DC6 achieved a drug release of 98.45% in phosphate buffer (pH 6.8), confirming its suitability for immediate therapeutic action. Thus, crospovidone proved to be the most effective superdisintegrant for formulating salbutamol sulphate MDTs, offering patient-friendly dosage form with faster disintegration and enhanced dissolution profile, particularly beneficial for asthmatic patients requiring quick relief.
Funding
None
Conflict Of Interest
The authors declare no any conflict of interest.
REFERENCE
Mahesh Dhumal*, Monika Ingale, Vishnu Patil, Shantanu Mane, Mozes Durgawad, Dr. Amit Ingle, Achal Ghate, Prasad Duphare, Formulation and In-Vitro Evaluation of Mouth Dissolving Tablet of Salbutamol Sulphate, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 9, 2886-2895 https://doi.org/10.5281/zenodo.17197352
10.5281/zenodo.17197352
