Rheumatoid arthritis is an autoimmune and chronic inflammatory disorder that mostly affects the synovial joints and can promote both cartilage and bone tissue destruction.^1,2Piroxicam is belongs to NSAID which is used to treatment of arthritis, inflammatory and rheumatic disorders. Piroxicam act by inhibiting Cyclooxygenase 1 and 2 which are act as mediator for production of inflammatory prostaglandins^3,4

Oral drug delivery route is one of the most economical and convenient among other drug delivery systems. Children and the elderly Patients faces difficulties in swallowing of tablet and capsules. In such case cases oral therapy become inconvenient which leads to poor patient adherence and may delay in duration of therapy. Such types of issues can be overcome by development of Orodispersible tablets (OTDs) which can be dispersed or dissolved in the small volume of saliva and followed by swallowing with or without water. Additionally, ODTs have potential in enhancement of bioavailability due to faster dissolution rate ^5,6

Piroxicam is a BCS class Ⅱ drug with poor aqueous solubility and high permeability, Due to its poor solubility its absorption will become slow and which leads to delayed onset of action.^7,8

There is a need to improve aqueous solubility of Piroxicam. So important study is solid dispersion of Piroxicam was prepared by solvent evaporations methods using cyclodextrin as carrier.

Natural superdisintegrants viz. Banana powder, Locust bean gum, Karaya gum, and Guar gum etc. were used to as Fast disintegration of ODTs. Which show advantages like biocompatibility, lower production cost and more acceptability by the patients.

Hence, in present work an attempt was made to increase the dissolutions rate of Piroxicam by using solid dispersion techniques and by adding potential Natural superdisintegrants.

2. MATERIAL AND METHODS:

2.1 Material:

Piroxicam drug purchased from Yarrow chem Pharma Co. Mumbai, β- Cyclodextrin purchased from Tokyo Chemical Industry. Co. Ltd. Japan. Banana Fruits ware Purchased from Local fruits market, Locust bean purchased from Qvans cure lifesciences Co. Gurugram, Guar gum purchased from Genuine Chemical Co. Mumbai. Karaka gum purchased from Sigma Life Science Co. Ltd. Sangrur, Mannitol and Chloroform purchased from Loba Chemie Pvt.Ltd. Mumbai, Microcrystalline cellulose, Saccharin Sodium, Magnesium Sterate purchased from Research-Lab Fine Chem Industries. Mumbai. Talc purchased from Molychem Co. Ltd. Mumbai.

2.2 Methods:

Evaluation of Natural Polymers by Swelling index:

The swelling index characterizes the rate at which a tablet will dissolute and is also an indicative of the mechanism. The swelling index was determined using in house prepared banana powder, Locust bean gum, Guar gum and Karaya gum.etc. One gram of polymers was accurately weighed and transferred to a 25-ml measuring cylinder. The initial volume occupied by the powder was noted, and the volume was made up to 25 ml with distilled water. The cylinder was, shaken gently, and set aside for 24 h. The volume occupied by the gum sediment was noted after 24 h. are shown in Table no.4.

V₀- V_t

% Swelling index = ----------------- x 100

V₀

Where,

V₀ is the initial volume of the powder in a graduated cylinder and V_tis the volume occupied by the swollen gum after 24 h.⁹

Preparation of Piroxicam solid dispersion by solvent evaporation method:

Piroxicam and β-Cyclodextrin were dissolved in the molar ratio of 1:1, 1:2 and 1:3 in a minimum quantity of Chloroform. The resultant solution was stirred and solvent was removed by evaporation in an open beaker on magnetic stirrer at 40°C for 1hr. The residue so obtained was further dried in a hot air oven at 60°C and stored overnight. The dried mass was sieved through sieve no.40.¹⁰

Solubility determination of Piroxicam solid dispersion:

Solubility determination of Piroxicam solid dispersion was carried out in 6.8 Buffer solution at 352nm. The solubility data of solid dispersion are shown in Table no.1

Table 1: Solubility study of meloxicam solid dispersion

Formul ation No.	Carrier	Ratio	Avg. solubility (µg/ml)	% Assy
SD 1	β- Cyclodextrin	1:1	4.80	96
SD 2	β- Cyclodextrin	1:2	5.1	103.9
SD 3	β- Cyclodextrin	1:3	5.4	108

Drug and Excipients Compatibility studies:

Compatibility of Piroxicam with excipients used was carried out by DSC and FTIR study.¹³

Formulation of solid dispersion into Orodispersible tablets:

The solid dispersion formulation SD3 Table 1. Was selected for tablet preparation as it showed enhanced solubility in comparison with other formulations. Compositions of Orodispersible tablet formulations are given in Table 2. The calculated amount of ingredients like Homebanana powder, Locusst bean gum, Guar gum, Karaya gum, mannitol, Avicel–102, and sodium saccharin, was taken in a mortar and pestle and mixed together. This powder blend passed through sieve no 40. After that, lubricating blend magnesium stearate were added within the powder blend. Then, this powder blend was subjected to direct compression using two tones pressure. The concentration of superdisintegrants used was 3% and 5% w/w in all formulations. The F1 to F8 formulations were prepared with a combination of natural polymers (superdisintegrant). F9 Formulation were prepared without polymer. (Superdisintegrants) The prepared tablets were further evaluated for DT, thickness, hardness, and weight variation¹¹

Table no. 2 Composition of Solid dispersion of Piroxicam Orodispersible Tablet

Sr. No	Ingredients	F1	F2	F3	F4	F5	F6	F7	F8	F9
1	Piroxicam (SD)	80	80	80	80	80	80	80	80	80
2	Banana Powder	6.68	10.68	-	-	-	-	-	-	-
3	Locust Bean Gum	-	-	6.68	10.68	-	-	-	-	-
4	Guar Gum	-	-	-	-	6.68	10.68	-	-	-
5	Gum Karaya	-	-	-	-	-	-	6.68	10.68	-
6	Microcrystalline Cellulose	68	64	68	64	68	64	68	64	74.68
7	Mannitol	38.66	38.66	38.66	38.66	38.66	38.66	38.66	38.66	38.66
8	Sodium Saccharin	5.33	5.33	5.33	5.33	5.33	5.33	5.33	5.33	5.33
9	Magnesium Stearate	1.33	1.33	1.33	1.33	1.33	1.33	1.33	1.33	1.33
Total Weight (mg)	200	200	200	200	200	200	200	200	200	200

Pre-Compression and Post-Compression Evaluation Study of Formulation:

Pre-compression study: Flow ability and compatibility of powder blend were analyzed using the parameters like Bulk density, tapped density, Hausner’s ratio, Compressibility index, and Angle of repose and the results are mentioned in Tables no.4 ¹²

1. Bulk density – it is calculated by the following formula

Mass

Bulk density =-------------

Bulk Volume

2. Tapped density – it is calculated by the following formula,

Mass

Tapped density = -------------

Tapped Volume

3. Hausner’s ratio – it is determined by the following formula

Tapped density

Hausner’s ratio = -------------------------

Bulk density

4. % Compressibility index (Carr’s index) – it indicates powder flow properties. The formula is given below,

Tapped density- Bulk density

% Compressibility = ---------------------------------- X 100

index Tapped density

5. Angle of repose – it is calculated using the following formula, h

Tan θ = ---------

Whare,

h = height of the powder cone, r = radius of the powder cone

Post-Compression Evaluation Study:

The prepared tablets were evaluated for thickness, diameter, weight variation, hardness, friability, disintegration time, wetting time and drug content as per standard procedures. Monsanto hardness tester (Scientific Engineering Corporation, India) was used for the determination of tablet hardness. The friability of the tablets was determined by Roche's friabilator (Veego, India). The disintegration time was measured by USP XXIV (Type Ⅱ Paddle type) test apparatus (Electrolab Pvt. Ltd). And the results are mentioned in Tables no. 5 ^13,14

1. Thickness:

Tablet thickness was measured using digital Vernier callipers. The range varies ± 0.03% using ten tablets.

2. Tablet hardness:

The hardness of tablet was determined using Monsanto or Pfizer hardness tester.

3. Weight variation test:

In weight variation test, twenty tablets were selected randomly, weighed on a digital weighing balance (and average weight was calculated. Then individual tablets were weighed and the weight was compared with the average weight.

4. Friability test:

Friability test is a very important test that is used to check strength for the transportation of tablets. It was measured by tablet friability tester (Roche's friabilator). Twenty initial weighted tablets (W initial) placed into the friability tester. Apparatus get started to make 100 rpm for 4 min (25 rpm/min). After completion of 4 min, the final weight of the tablet was taken (W final). Pharmacopeial limit is percent friability should not more than 1%. Percent friability of a tablet was calculated by the following formula,

W₁– W₂

% F = --------------------- X 100

W₁

Where,

W₁: Weight of the tablets before friability test,

W₂: Weight of the tablets after friability test

5. Disintegration test:

The in vitro disintegration tests of the tablets (n = 6) were performed using a disintegration tester (Electrolab, model ED-2L, India) containing distilled water which was maintained at 37 ± 2°C (10). One tablet was placed in each of the six tubes of the basket and discs were added.

6. Wetting time:

A piece of tissue paper folded twice was placed in a small petridish (ID=6.5 cm) containing 6 ml of simulated saliva pH 6.8, a tablet was put on the paper, and the time for complete wetting was measured.

7. Estimation of drug Content:

For determination of drug content, a total 10 tablet were weighed and powder equivalent to 20 mg of Piroxicam was weighed and dissolved pH 6.8 phosphate buffer then filtered through whatman filter paper, and solution was analyzed for Piroxicam content by UV-Spectrophotometer at 352nm using as blank pH 6.8 phosphate buffer.

8. In vitro dissolution study:

Percentage cumulative drug release of Piroxicam ODTs was determined by United States Pharmacopeia Type II dissolution tester apparatus (Lab India Disso II) using the paddle method. The dissolution test was performed using 900 ml of phosphate buffer pH 6.8 at 37°C placed into the basket. A sample of 5 ml solution was withdrawn from the dissolution apparatus at a regular gap of 2 min for 10 min and placed into a 10 ml volumetric flask. The same quantity of the sample was replaced with a fresh dissolution medium by phosphate buffer (pH 6.8). The absorbance of these samples was analyzed at 352 nm using a UV spectrophotometer. And the results are mentioned in Tables no. 5

RESULT:

A) Identification of drug:

1) Melting point:

The melting point was determined by the capillary method; it was observed at 206°C to 208°C (standard melting point – 210°C). It gave authentication of pure drug.

2) DSC (Pure drug):

DSC analysis was performed to evaluate the thermal behaviour of Piroxicam. The Piroxicam shows a sharp endothermic peak due to the melting of a drug at 205°C corresponding reported to the melting point of the pure drug at 205°C. The sharp endothermic peak shows the crystalline nature of the drug. DSC of the pure drug is shown in Fig. 1.

Fig 1: DSC Thermgraph of pure Piroxicam

3) FTIR spectrum of Piroxicam:

The FTIR graph was derived for the identification of the various functional groups. The FTIR spectra of piroxicam consisted of many sharp peaks that confirm the crystalline nature of the drug. The observed FTIR peaks of piroxicam were matching with the reported peaks, it was confirmed that the obtained sample is of Piroxicam and is in pure form as shown in Fig.2 and Table 3.

Fig 2: FTIR spectrum of Piroxicam

Table 3: Functional group along with their wave numbers

Groups	Wavenumber (cm^-1)
N-H stretch	3334
SO2 stretch	1147
C-S stretch	689
C-C stretch	1529

4) Solubility of Piroxicam:

Sparingly soluble in water, dilute acid, and most organic solvents. It is slightly soluble in alcohol and in aqueous solutions. The practical solubility of Piroxicam in water was found to be 10.73 mg per 100 ml.

5) UV spectroscopy (Determination of λ max and calibration curve):

The λ max and calibration curve was determined by UV–spectrometer. The λ max in a 6.8 phosphate buffer solution was found to be at 352nm. As mention in Fig. 2. And Calibration curve prepared in a 6.8 phosphate buffer solution at 352nm. The data had a correlation coefficient R²=0.9985. These results indicate that there is a linear relationship between concentration (2–10µg/ml) and absorbance, as mention in Fig. 3,4

Fig. 3: λ max of Piroxicam in pH 6.8 Phosphate buffer.

Fig 4: Calibration curve of Piroxicam in pH 6.8Phosphate buffer

B) Evaluation of polymers:

The swelling index of homemade banana powder, Locust bean gum, karaya gum, and Guar gum showing in table 4.

Table No: 4 swelling index of Natural polymers

Polymer Name	Swelling index (%)
Homemade Banana Powder	58.33
Locust bean gum	21.15
Guar gum	27.15
Karaya Gum	19.38

C) Drug excipient compatibility study:

1) DSC:

Compatibility of Piroxicam with excipients used was carried out by DSC study. The DSC thermogram obtained for drug and excipient mixture samples is as shown in fig.no.4. The DSC study shows the endothermic peak at 170.43⁰C of azathioprine which confirms that there is no interaction between drug and excipients used.

Fig: 5 DSC thermograms of Piroxicam + Excipients

2) FTIR Study:

FTIR study was carried out to check the compatibility of drug with the excipients used in formulation and it is shown in fig.5

Table no. 5 Physical parameters of powder blends of Piroxicam Orodispersible tablet.

Formulation Code	Bulk density (mg/ml)	Tapped density (mg/ml)	Angle of repose (θ)	Hausner’s ratio	Carr’s Index (%)
F 1	0.43	0.50	35.37	1.16	14
F 2	0.43	0.51	35.36	1.16	14.01
F 3	0.41	0.48	34.43	1.17	14.58
F 4	0.43	0.50	35.41	1.16	14
F 5	0.42	0.49	31.41	1.16	14.28
F 6	0.43	0.48	36.44	1.16	14
F 7	0.42	0.49	35.37	1.16	14.25
F 8	0.41	0.48	37.45	1.17	14.59
F9	0.43	0.50	38.46	1.16	14.02

Table no. 6 Characterization of formulated Orodispersible tablet

Formulation code	Hardness Kg/cm²	Thickness (mm)	Friability (%)	Weight Variation (%)	Wetting time in Sec.	Disintegration time in Sec.
F1	1.5 ± 0.29	0.4 ± 0.01	0.78	198 ± 0.04	58	59
F2	1.5 ± 0.25	0.4 ± 0.03	0.76	199 ± 0.07	54	57
F3	1.4 ± 0.27	0.5 ± 0.02	0.78	197 ± 0.08	94	96
F4	1.5 ± 0.35	0.4 ± 0.01	0.77	200 ± 0.07	99	98
F5	1.4 ± 0.25	0.4 ± 0.03	0.76	197 ± 0.03	119	120
F6	1.5 ± 0.29	0.5 ± 0.02	0.77	199 ± 0.04	131	135
F7	1.5 ± 0.25	0.5 ± 0.01	0.78	199 ± 0.03	128	130
F8	1.6 ± 0.27	0.4 ±0.03	0.78	198 ± 0.01	133	140
F9	1.5 ± 0.29	0.5 ± 0.02	0.80	200 ± 0.02	139	145

Table no.7 In-vitro drug release of Piroxicam Orodispersible tablet

Formulation code				% CDR
Formulation code	00 sec.	10 sec.	20 sec.	30 sec.	40 sec.	50 sec.	60 sec.
F1	0	65.66	71.20	75.50	82.78	87.387	99.12
F2	0	70.34	78.79	85.28	84.87	93.57	99.17
F3	0	66.88	70.24	75.30	81.47	88.41	98.25
F4	0	57	65.13	78.66	83	92.48	98.13
F5	0	64.11	70.32	78.20	81.78	90.31	96.35
F6	0	56	75.12	80.60	87.54	94.15	96.67
F7	0	73.81	79.81	81.57	86.21	90.63	97.34
F8	0	69.39	74.42	81.89	88.89	89.90	94.26
F9	0	23.64	29.97	34.31	43.01	49.44	56.18

Fig. no. 7. In-vitro Release Profile of Piroxicam Orodispersible tablet F1 to F9

CONCLUSIONS:

Based on result obtained, it can be concluded that solid dispersion using Beta- Cyclodextrin is an effective technique to increases solubility of Piroxicam. Further use of natural polymer like banana powder as superdisintegrant in ODTs of Piroxicam is a promising and economically affordable approach for geriatric patients.

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Received on 28.09.2024 Revised on 25.11.2024

Accepted on 03.01.2025 Published on 27.02.2025

Available online from March 05, 2025

Asian J. Pharm. Tech. 2025; 15(1):6-12.

DOI: 10.52711/2231-5713.2025.00002

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