INTRODUCTION:

The oral mucosa is a promising medium for drug delivery, When a drug with a high first-pass Metabolisum is intended to have a quick onset of action or increased bioavailability. Hence, there is a developing interest in designing alternative dose forms, such as orally fast dissolving Tablet.

Loratadine is a white, hygroscopic powder with the molecular weight 382.88 and chemical formula C22H23ClN2O2. Loratadine is a second-generation H1histamine antagonist drug used to treat allergy conditions like hay fever. Loratadine is a second-generation H1histamine antagonist drug used to treat allergy conditions like hay fever¹.

It is used to treat skin disorders, such as atopic dermatitis and urticaria, allergic rhinitis, acute coryza, and ocular allergies, at doses of 10mg once day for adults and 5 mg or 10mg for children aged 2 to 12 who weigh less than 30kg. The main objective of study is to make loratadine more easily soluble by using superdisintegrants as carriers, prepare and perfect fast-dissolving tablets containing different superdisintegrants. to improve the drug's molecule's safety and effectiveness, obtain improved compliance, rapid up its onset of action, and develop a stable dose form.^2-3

METHODS AND MATERIALS:

Materials:

Vasudha Pharmaceutical ltd¸supplied loratadine as a gift sample.While sodium starch glycolate, crospovidone, croscarmellose sodium, and sodium starch glycolate were purchased from Fine Chemicals, Mumbai, Maharashtra, India, Every other substance, including reagents,was of analytical grade.

Instrumentation:

The tablet compression machine (Model no. 8 station, D, Cemach Machinaries Ltd.) and the UV visible spectrophotometer (Model EQ-826, Equiptronics) were the objects of the work. The Fourier Transform Infrared Spectrophotometer (Bruker) secured the FTIR spectra of API and its excipients. Wenser PGB220 electronic precision balance was used for every weighing.

Methods:

Formulation of Tablets:

Three different super disintegrants, including Crosscarmilose sodium, Sodium starch glycollate, and Crosspovidone, were used to create the MDTs for loratadine utilising the direct compression method in the ratios of 5.2, 5.3 and 5.4 A mixture of Aerosil and magnesium stearate was used as a glidant and lubricant, respectively, along with mannitol as a diluent. All ingredients and the right amount of the medicine were weighed according with the formula mentioned in Table No. 1. All ingredients, including the right quantity of the ingredients, were weighed according with the formula in Table 1, and all powders, with the exception of Aerosil and magnesium sterate, were homogeneously mixed in a mortar and pestle for 15 minutes. The prepared powder mixture was passed through sieve #60. Finally, Aerosil and magnesium sterate that had passed through filter #30 were added and mixed for an additional 10 minutes. A 200 mg homogeneously mixed powder blend that was accurately measured was physically fed, and 8 stations were used for breaking it with consistent compression force and hardness. Tablet compression machine by Cadmach with 9 mm, flat punches ^4-5

Table No: 0.1- Formulation of Loratadine loaded ODTs

S. No	Ingredients (mg/tab)	Formulation code
S. No	Ingredients (mg/tab)	F1	F2	F3	F4	F5	F6	F7	F8	F9
1	Loratadine	10	10	10	10	10	10	10	10	10
2	Croscarmellose sodium (Ac-di-sol)	4	6	8	-	-	-	-	-	-
3	Sodium starch glycollate (Explotab)	-	-	-	4	6	8	-	-	-
4	Crospovidone (Polyplasdone)	-	-	-	-	-	-	4	6	8
5	Micro-crystalline cellulose	74	72	70	74	72	70	74	72	70
6	Mannitol	100	100	100	100	100	100	100	100	100
7	Aerosil	4	4	4	4	4	4	4	4	4
8	Aspartame	6	6	6	6	6	6	6	6	6
9	Magnesium stearate	2	2	2	2	2	2	2	2	2
10	Strawberry flavour	q.s	q.s	q.s	q.s	q.s	q.s	q.s	q.s	q.s
11	Total	200	200	200	200	200	200	200	200	200

By Preparation of the Standard Curve:

10mg of loratadine was measured, divided among three 100ml standard flasks, and brought to the proper concentration using methanol, 0.1N HCL, and Phosphate Buffer pH 6.4 individually. To acquire the concentration of 10g/ml of each solution, take 1ml from each of the above solutions and combine them in a 10ml standard flask. A scan in the range is 200 to 400nm was performed on each blank to identify the drug's maximum absorption, 0.1N HCl absorbs at 247.5nm.

Determination of drug-polymer compatibility:

By Fourier Transforms Infra-Red (FTIR) Spectroscopy:

The detection of a possible chemical reaction between the medication and the superdisintegrants required an approach called infrared spectra matching. A physical mixture (1:1) of the drug and the superdisintegrants was made and combined with the appropriate amount of potassium bromide. A transparent pellet was created from 100mg of this combination by compressing it under 10 tonnes of pressure in a hydraulic press. It was scanned with a Parkin elmer- Pharmaspec-1 FTIR Spectrophotometer from 4000 to 400 cm-1.⁶

By Differential Scanning Calorimetry Study (DSC):

the superdisintegrants should be made in connection to the drug delivery and the compatibility with the same drug, therefore it is essential to assess any potential interactions between the active principle and the superdisintegrants when formulating drugs.related to the final product's stability. The physical mixture created by mixing loratadine powder in a 1:1 ratio with several superdisintegrants was stored in tightly closed glass vials.

Evaluation of Powder Blends of Loratadine:

Bulk density:

According to the reported strategy, bulk density was calculated using the formula shown in Figure:

BD = Weight of the powder/Volume of the powder.

Tapped density:

Following repeated taps on the previously studied measuring cylinder, the true volume and true density of the object was determined using the formulas below.⁷

TBD = Weight of the powder/Tapped volume of the powder.

Compressibility index, or Carr's index:

The following formula was used to calculate it using the earlier calculated bulk,density true densities.⁷

Carr’s index (%) = (tapped density-bulk density)/tapped density*100.

Hausner's ratio:

Hausner's ratio is an indirect index of powder flow. It is calculated by the following formula:

Hausner's ratio= ρt /ρb Ρt : bulk density

Ρb : tapped density Angle of repose:

The reported method1 and angle of repose were used to determine a granules' flow characteristic used the behind equation to determine.

θ = tan-1(h/r)

Fast dissolving tablet evaluation:

Tablets were evaluated for an assortment of QC factors, including appearance, weight variation, tablet hardness, and furthermore.test for content uniformity, thickness, friability, water absorption ratio, disintegration time, dissolution rate, and dispersion time⁸.

RESULT AND DISCUSSION:

Loratadine by using 0.1 N HCl. UV absorption spectrum of Loratadine in 0.1N HCl shows λmax at 247.5nm. Absorbance obtained for various concentrations of Loratadine in 0.1N HCl are given in table 8.4.The graph of absorbance vs. concentration for Loratadine was found to be linear in the concentration range of 10μg /ml. The drug obeys Beer- Lambert’s law in the range of 10 μg/ml⁹.

Table No.0.1.Absorbance of Loratadine

Sr. No.	Concentration (In ppm)	Absorbance
1.	5	0.186
2.	10	0.339
3.	15	0.527
4.	20	0.663
5.	25	0.879
6.	30	1.050

Fig.0.1. Absorbance of Loratadine

By Fourier Transforms Infra-Red (FTIR) Spectroscopy:

Major functional groups present in Loratadine show characteristic peaks in IR spectrum. Table No.0.2.shows peaks observed at different wave numbers and the functional group associated with these peaks.The major peaks are identical to functional group of Loratadine. Hence, the sample was confirmed as Loratadine.

Observation :

In FTIR studies there was no appearance or disappearance of the Principal peaks in the superdisintegrants drug mixture, which confirmed the absence of any chemical incompatibility between the drug and the superdisintegrants.

By Differential Scanning Calorimetry Study (DSC):

The compatibility and interactions between drug and polymer were checked using differential scanning calorimetry results obtained were shown in Figures

Table 0.2. DSC thermogram parameters of Loratadine with various polymers

Sr. No.	DSC thermogram	Onset temperature (°C)	Peak temperature (°C)	End set temperature (°C)
1	Loratadine	134.13	139.56	148.00
2	Loratadine + CCS	134.17	140.32	154.55
3	Loratadine+ SSG	135.66	141.26	149.67
4	Loratadine + CP	135.75	140.55	149.16

According, DSC thermogram showed that there was no major difference in onset temperature, end set temperature and peak temperature when compared with pure drug thermogram. Therefore it could indicate that there was no incompatibility between drug and different polymers.

In –Vitro Dissolution Studies:

Fig no.0.3. Disintegration expressed

Formulations varied from 12±1.8973 to 30±1.8973 seconds.¹³ The rapid disintegrate was seen in the formulations containing Crospovidone and Croscarmellose sodium. This is due to rapid intake of the water from the medium, swelling and burst effect. It also noticed that the concentration of Croscarmellose sodium followed by Crospovidone and Sodium starch glycollate increased, time taken for disintegrate was reduced.¹⁴

Reveals that the formulations with highest concentration of Croscarmellose sodium with Crospovidone shown significant rapid disintegrate. Disintegrate time was to be found very less for F9 formulation which contains highest concentration and efficiency of Crosspovidone.

CONCLUSION:

Mouth dissolving tablet of Loratadine can be successfully prepared using selected different superdisintegrants, diluents and taste inhibiting agents by sensory approach using Direct Compression method.¹⁵

Formulation F9 revealed promising results which was formulated by Crosspovidone in 5:4 ratio. This formulation exhibited highest disintegrate time and highest percent drug release which provides quick onset of action and immediate relief in suddenly arising allergic reactions. Moreover, they showed pleasant mouth feel. This formulation satisfied all the tablet evaluation parameters for Mouth Dissolving Drug Delivery System. Hence, it was concluded that the F9 Formulation is optimized formulation amongst F1 to F9.

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Received on 15.01.2024 Modified on 02.03.2024

Res. J. Pharma. Dosage Forms and Tech.2024; 16(2):133-136.

DOI: 10.52711/0975-4377.2024.00021