INTRODUCTION:

The most common and favoured way to deliver drugs is through the oral route because it is practical and easy to use. For patients, taking medicine in the tablet or pill form is a convenient and familiar method, which ensures they comply with the treatment, making it more effective than other administration methods such as injection. Although the oral route is preferred due to its practicality, it may not be the most efficient delivery method for some drugs.

There are the major issues that could arise is poor absorption, leading to low bioavailability, which is the most significant problem¹. A type of solid product known as a solid dispersion contains two or more separate components, often an inerthydrophilic material and a hydrophobic medication like the proton pump inhibitor Lansoprazole, which isclassified as a BCS Class II medicine. Drugs that are poor in water solubility yet high in permeability acrossmembranes are classified as BCS Class II drugs. In order to increase the oral absorption and bioavailability ofBCS Class II medications, a continuous spread method is ideal. In solid dispersion, the drug is dispersedthroughout a matrix made up of both hydrophilic and hydrophobic components, producing a solid dispersion².

Solubility:

· Or put another way, solubility is the ability of a substance to form a solution with another substance.

· The solute is the substance that needs to dissolve, and the solvent is the substance that the solute dissolves in to create a solution. When the solvent is water, a substance that has been dissolved in it is called a solution or hydration.

· In other words, most drugs are administered orally, and their effectiveness is greatly influenced by how well they dissolve in water. Since 1995, over 90% of approved drugs have had low solubility have low water solubility, which means that their absorption, bioavailability, and pharmacokinetic profile can be difficult to predict. In fact, roughly 40% of drugs that are newly discovered through combined screening programs used by pharmaceutical companies are believed to have low solubility in water.

· Solubility plays a critical role in achieving the desired concentration of a drug in the systemic circulation, which is necessary for the drug to have the desired effect.

· Therefore, when developing an oral drug formulation with low water solubility, improving solubility is an essential factor to consider³.

METHODS AND MATERIALS:

Materials:

Lansoprazole is obtained from Balaji Drugs in Nashik, Maharashtra, India, and purchased Polyethylene glycol 6000 from Fine Chemicals in Mumbai, Maharashtra, India. They obtained all other reagents from their research lab.

Instrumentation:

Usedvarious instruments for research work, including a UV-visible spectrophotometer (Equiptronics, model EQ-826) and a tablet compression machine (Cemach Machinaries Ltd, model no. 8 station D). They also used a Fourier Transform Infrared Spectrophotometer (Bruker) to obtain FTIR spectra of the API and its excipients, and an electronic precision balance (Wenser PGB220) for all weighing.

Methods:

Preparation of Solid Dispersion by Solvent Evaporation Method:

Solid dispersion was prepared by using solvent evaporation method. In this method, drug and polymer is dissolve in common organic solvent then solvent is evaporated at low temperature. Remained blend is milled through subsequent screen⁴.

Formulation and Development:

Preparation of Solid Dispersion:

To prepare a solid dispersion of lansoprazole, used the solvent evaporation method. First, they dissolved lansoprazole in methanol to create a clear solution. Then, they added different polymers (PVP K30, PEG 6000, and Poloxamer 407) to the solution at various ratios (1:1, 1:2, and 1:3). After dissolving the polymers, they removed the solvent by evaporation on a water bath at 60°C. The resulting dry mass was stored in a desiccator until a constant mass was obtained. Finally, the solid dispersion was obtained by passing the dry mass through a #40 sieve⁵.

Table 1.0 Formula for Lansoprazole Solid Dispersion

Sr. No.	Batch Code	Ratio	Drug	Polymer
1.	SD1	1:1	Lansoprazole	PVP K30
2.	SD2	1:2	Lansoprazole	PVP K30
3.	SD3	1:3	Lansoprazole	PVP K30
4.	SD4	1:1	Lansoprazole	PEG 6000
5.	SD5	1:2	Lansoprazole	PEG 6000
6.	SD6	1:3	Lansoprazole	PEG 6000
7	SD7	1:1	Lansoprazole	Poloxamer 407
8.	SD8	1:2	Lansoprazole	Poloxamer 407
9.	SD9	1:3	Lansoprazole	Poloxamer 407

Formulation and Evaluation of Lansoprazole Tablet:

One the dispersion was formulated; it was very important to convert them into a suitabledosage form with respected to ease of manufacturing the dosage form and its use tablets are widely accepted as dosage forms due to their stability, easy and economic commercialization as well as convenience to the patient. In the present work under taken, the possibility of developing dissolving tablet of Ibuprofen, which is fast reproducible and complete drug dissolution using dispersion technology. It was attempted to dissolving tablets with dissolution using solid dispersion technology.

Formulation of Lansoprazole Tablet:

In this study, we aimed to develop dissolving tablets of lansoprazole using solid dispersion technology to achieve reproducible and complete drug dissolution. The solid dispersion was compressed with tablet excipients such as Crospovidone, Sodium Starch Glycolate, Microcrystalline Cellulose, Sodium Saccharin, Magnesium Stearate, Talc, and lactose on a direct compression machine with an 8.00mm concave punch. Super disintegrants such as SSG, Crospovidone and MCC were used at varying concentrations (2% to 6%, 2.5% to 7.5%, and 5% to 15%) to prepare tablets. The selection was based on disintegration time and in vitro release study. Details of the different formulations are shown in the table⁶.

Table 2.0 Formulation Table for Lansoprazole Tablet

Ingredients	F1	F2	F3	F4	F5	F6	F7	F8
SD6 (1:3)	120	120	120	120	120	120	120	120
Crospovidone	8	4	4	12	8	8	4	12
SSG	10	15	10	10	10	15	10	5
MCC	20	20	10	10	20	30	30	20
Na. Saccharine	10	10	10	10	10	10	10	10
Mg. Stearate	4	4	4	4	4	4	4	4
Talc	3	3	3	3	3	3	3	3
Lactose	Upto 200mg	Upto 200mg	Upto 200mg	Upto 200mg	Upto 200mg	Upto 200mg	Upto 200mg	Upto 200mg

F9	F10	F11	F12	F13	F14	F15	F16	F17
120	120	120	120	120	120	120	120	120
8	8	8	12	8	4	8	12	8
5	10	5	15	15	5	10	10	10
30	20	10	20	10	20	20	30	20
10	10	10	10	10	10	10	10	10
4	4	4	4	4	4	4	4	4
3	3	3	3	3	3	3	3	3
Upto 200mg	Upto 200mg	Upto 200mg	Upto 200mg	Upto 200mg	Upto 200mg	Upto 200mg	Upto 200mg	Upto 200mg

RESULT AND DISCUSSION:

Characterization of physicochemical properties of drug:

Organoleptic properties:

Lansoprazole has yellowish, odorless and tasteless amorphous powder that the entire drug characteristic complies with official standards.

Pre-formulation study:

Determination of Physical constant (Melting Point):

The melting point was determined by capillary method and it was found to be in range of 168- 172⁰C which complies with I.P.

Solubility profile of drug:

The solubility of the Lansoprazole was determined by using the Shake flask method with the help of various solvents like water, methanol, Chloroform, 0.1N HCL and 0.1N NaOH It was found to be soluble in methanol while insoluble in water.

Analysis of drug:

Calibration Curve Method:

The calibration curve of Lansoprazole was performed in methanol. The absorbance of the solution was measured at 284nm using UV-visible spectrophotometer⁷.

· Line Equation: y=0.0404x+0.0187

· Regression Coefficient: R²=0.9841

Table 3.0 Concentration and Absorbance

Sr. No.	Concentration (In ppm)	Absorbance
1.	2	0.157
2.	4	0.167
3.	6	0.233
4.	8	0.310
5.	10	0.424
6.	12	0.502
7.	14	0.599
8.	16	0.622
9.	18	0.729
10.	20	0.863

Fig. 1.0 Calibration curve of Lansoprazole.

Stability study of Lansoprazole with excipients:

Physical Observation:

All the physical mixture of lansoprazole drug and excipients observed physically for compatibility study.

Table 3.0 Compatibility Study of Lansoprazole and Excipients

Sr. No.	Composition	Caking	Liquification	Discoloration	Odour	Conclusion
1.	Drug + PEG 6000	No	No	No	No	Compatible
2.	Drug +Crospovidone	No	No	No	No	Compatible
3.	Drug + SSG	No	No	No	No	Compatible
4.	Drug +MCC	No	No	No	No	Compatible
5.	Drug + Sodium Saccharine	No	No	No	No	Compatible
6.	Drug + Magnesium Stearate	No	No	No	No	Compatible
7.	Drug +Talc	No	No	No	No	Compatible
8.	Drug +Lactose	No	No	No	No	Compatible

DSC study:

Differential Scanning Calorimetry (DSC) is thermal analytical technique that measures the heat against time and check the how physical properties of sample changes with increasing temperature with time⁹.

Differential Scanning Calorimetry of Lansoprazole:

Thermal analysis of Lansoprazole is carried using DSC. The DSC curve of Lansoprazole shows sharp exothermic peak at 169.21⁰C at 14.10min.

Fig 4.0 Differential Scanning Calorimetry of Lansoprazole

Differential Scanning Calorimetry of Lansoprazole and All Excipients:

Fig 5.0 Differential Scanning Calorimetry of Lansoprazole and all Excipients

Solubility of Solid Dispersions of Lansoprazole:

Solubility measurements were performed using the method of Higuchi and Connors (1965). An excess amount of Solid Dispersion of Lansoprazole was weighted in test tubes to which was added 10ml of distilled water, also Lansoprazole containing various concentration of PVP K30, PEG 6000 and Poloxamer 407 the sample were sonicated for 1hr. at room temp. Thereafter, the capped test tube was filtered through a 0.4 membrane filter, and the filtered solution were analyzed for Lansoprazole at 284nm by UV-Visible spectrophotometer¹⁰.

Fig. 6.0: Solubility of Solid Dispersions of Lansoprazole.

Drug Content:

Equivalent to 30mg of Lansoprazole solid dispersion was weighed and dissolved in 100ml of methanol then filtered through Whatman filter paper. Solution was analysed for Lansoprazole content by UV Spectrophotometer at 284nm using methanol.

Percent Practical Yield:

Percentage practical yield was used to know about % yield or efficiency of any method and help in selection of appropriate method of production¹¹.

Fig 7.0 Percent Practical Yield/ Drug Content

Pre-Compression Evaluation:

Prior to compression, the formulation blend was evaluated for pre-compression parameters like bulk density, tapped density, hausner ratio, carr’s index and angle of repose¹².

Post Compression Evaluation:

After compression of tablets the formulated tablets is evaluated for post compression parameter like weight variation, diameter, thickness, hardness, friability and disintegration time¹³.

Table 5.0 Pre-Compression evaluation for Lansoprazole Tablet

Formulation code	Bulk density (gm/ml)	Tapped density	Hausner ratio	Carr’s index (%)	Angle of repose (θ)
F1	0.51	0.61	1.20	16.39	34.13
F2	0.50	0.60	1.20	16.66	33.69
F3	0.50	0.61	1.22	18.03	37.57
F4	0.50	0.59	1.18	15.25	33.25
F5	0.51	0.61	1.20	16.39	34.13
F6	0.51	0.60	1.18	15.00	33.69
F7	0.49	0.60	1.22	18.33	36.53
F8	0.50	0.60	1.20	16.67	36.53
F9	0.51	0.60	1.18	15.00	37.04
F10	0.51	0.61	1.20	16.39	34.13
F11	0.50	0.60	1.20	16.67	36.53
F12	0.50	0.56	1.12	10.71	33.52
F13	0.51	0.59	1.16	13.56	34.13
F14	0.50	0.58	1.16	13.79	34.59
F15	0.51	0.61	1.20	16.39	34.13
F16	0.49	0.58	1.18	15.52	34.59
F17	0.51	0.61	1.20	16.39	34.13

Table 6.0 Post Compression evaluation for Lansoprazole Tablet

Formulation code	Weight Variation (mg)	Diameter (mm)	Thickness (mm)	Hardness (kg/cm²)	Friability (%)	Disintegration time (min)
F1	202	8.00	4.00	5.2	0.5	27
F2	201.5	8.00	4.01	5.6	1.0	27
F3	201.5	8.00	4.02	5.4	0.98	28
F4	202	8.00	4.00	4.4	0.97	24
F5	202	8.00	4.00	5.2	0.5	27
F6	202	8.00	4.02	5.4	0.49	25
F7	203	8.00	4.05	4.8	0.98	30
F8	196.5	8.00	4.00	5.1	0.51	29
F9	202.5	8.00	3.97	4.9	0.99	28
F10	202	8.00	4.00	5.2	0.5	27
F11	204	8.00	4.03	4.3	0.97	30
F12	201	8.00	4.00	4.3	0.5	20
F13	202.5	8.00	4.00	4.8	0.99	21
F14	201.5	8.00	4.00	4.2	0.99	32
F15	202	8.00	4.00	5.2	0.5	27
F16	198	8.00	3.98	5.1	0.51	26
F17	202	8.00	4.00	5.2	0.5	27

Table 7.0 In-Vitro % Drug Release of Lansoprazole in Phosphate Buffer 6.8

Time (min.)	F1	F2	F3	F4	F5	F6	F7	F8
0	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00
5	14.28	16.43	13.31	19.18	14.28	19.40	12.65	13.54
10	25.71	27.42	20.07	31.43	25.71	34.11	26.23	27.72
15	34.48	37.45	25.05	37.67	34.48	38.04	29.43	31.14
20	45.17	49.77	37.74	53.93	45.17	47.25	37.15	39.38
25	53.93	52.30	47.84	56.16	53.93	61.06	45.47	53.64
30	59.35	61.06	54.38	58.83	59.35	65.66	53.56	57.20
35	68.49	71.23	64.99	74.87	68.49	75.10	66.037	65.52
40	75.24	79.03	70.94	88.76	75.24	87.20	72.94	80.22
45	86.46	87.65	79.25	93.59	86.46	93.73	78.66	82.60

F9	F10	F11	F12	F13	F14	F15	F16	F17
0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00
11.23	14.28	12.79	20.57	19.70	9.40	14.28	17.62	14.28
24.90	25.71	24.75	38.93	29.20	12.07	25.71	26.75	25.71
27.50	34.48	34.33	57.27	38.70	13.97	34.48	36.26	34.48
35.96	45.17	45.47	63.80	48.20	16.33	45.17	45.62	45.17
44.06	53.93	52.15	70.33	57.76	18.67	53.93	54.90	53.93
61.80	59.35	57.35	78.97	67.23	20.97	59.35	64.03	59.35
71.46	68.49	62.32	87.57	76.23	23.23	68.49	73.61	68.49
74.43	75.24	70.12	93.13	86.16	24.23	75.24	82.82	75.24
76.95	86.46	77.99	98.93	95.67	27.93	86.46	92.17	86.46

Fig 8.0 In Vitro Drug Release Batch F1 to F8

Fig 9.0 In Vitro Drug Release Batch F9 to F17

CONCLUSION:

The study of solubility enhancement of Lansoprazole by solid dispersion technique using different carriers shows the following conclusion, The solid dispersion which is prepared by solvent evaporation method were found to be white in colour, free flowing powders with uniform drug content.With FTIR spectroscopic studies shows the there was no interaction between Drug-Excipient.9 different formulations of solid dispersions (SD1-SD9) and found that SD6 showed the most promising results with a practical yield of 95.83%. Solid dispersion containing PEG 6000 showed better solubility compared to those containing PVP K30 and Poloxamer 407. By increasing the concentration of the carriers, the solubility of Lansoprazole was also found to increase. The In-vitro Drug release study of solid dispersions SD6 show the high drug release around 98.93%. Overall, in the all formulations F12 which contains 6%, 3.75% and 10% of Crospovidone, SSG and MCC release the 98.93% drug is the best formulation.

ACKNOWLEDGEMENT:

We express our gratitude to the teachers and Principal of Loknete Dr. J. D. Pawar College of Pharmacy, Manur, Tal. Kalwan, for their valuable guidance and support.

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Received on 02.05.2023 Modified on 09.07.2023

Res. J. Pharma. Dosage Forms and Tech.2023; 15(4):229-235.

DOI: 10.52711/0975-4377.2023.00037

Sr. No.	Wave number in formulation (cm-1)	Characteristic Wave number range cm-1	Bond nature and bond attributed
1.	1266.66	1200- 1300	S=O Stretching
2.	1579.65	1550- 1650	N-H Bending
3.	2983.51	3000- 3100	Aromatic C-H Stretching
4.	1454.09	1400- 1500	C-H Bending