Formulation And Evaluation of Bilayer Tablets of Teneligliptin by Using Liquid Solid Compact Technology

Abstract

Teneligliptin is an antidiabetic medication and belongs to BCS class II drugs. The present study aims at the preparation of liquisolid compact of teneligliptin with an aim to improve the solubility of the drug. The liquid solid system uses a non-volatile solvent to dissolve the drug. The drug's suspension or solution is transformed into a free-flowing, dry, and compressible powder by mixing it with a statistically determined amount of coating and carrier material. In this study Microcrystalline cellulose and Aerosil were used as carrier and coating material respectively. The non-volatile solvent that was used is propylene glycol. Nine formulations with varying excipient ratios were created, and their flowability and compressibility were assessed. A study on the interaction between drugs and excipients was conducted using Fourier transform infrared spectroscopy (FTIR). The optimized formulations were evaluated for flowability, compressibility study, comparative dissolution study with pure drug. The improved formulations exhibited good compression characteristics and flow properties. The medication and excipient did not physically interact, according to the FTIR analysis. The comparative dissolution study of the optimized formulations with the pure drug revealed significant improvement of solubility of teneligliptin in liquid solid compact. The diffusion exponent (n) of Korsmeyer-peppas model was found to be non-fickian. The results showed that liquid solid had illustrated significantly higher drug release rates than those of expectedly made was due to an increment in wetting properties and surface of sedate accessible for disintegration. Therefore, it can be concluded that a free flowing, non-adherent, dry and compressible powder of teneligliptin can be prepared using liquid solid compact technology.

Keywords

Liquisolid Compacts; Teneligliptin; In vitro studies; Drug release kinetics; Dissolution rate.

Introduction

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EXPERIMENTAL WORK

       
           
       
Fig 1: Preparation Liquidsolid compact

6. Formulation Of Teneligliptin Bilayer Tablets

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8. Evaluationoftablets: (Postcompression Parameter)

1. 1. 1. 1. Weight variation
         2. Thickness
         3. Hardness
         4. Assay of formulations
         5. Friability
         6. Disintegration Time
         7. Dissolution
         8. Stability studies
1. Weight Variation: A random selection of twenty tablets was weighed, and the average weight was ascertained. The specific weight of each pill was determined. According to USP regulations, no tablet weight may be less than 90% or more than 110% of the average weight.
2. Thickness: Three tablets are randomly selected from each formulation and thickness is measured individually by vernier caliper. It is expressed in millimeter (mm) and average is calculated.
3. Hardness: Take 10 tablets containing the substance that was provided for analysis. Calculate the Hardness in kg/cm2 for every tablet and note the results. Determine the average result by averaging the ten measurements.

Acceptance criteria: Not less than 4.0Kg/cm2

4. Friability (core tablets): Take thirteen tablets from the sample that was provided for analysis and dedusting. Once the tablets have been weighed, note the outcome. Once the tablets have been inserted into the drum of the friability equipment, turn the device on for four minutes, or one hundred rotations. Run the device for the specified duration or rpm. After taking out the tablets, dust off.

 Weigh the tablets and calculate the friability by the following formulae.

Acceptance criteria: Friability is not more than 1.0%

5. Assay of the Formulations: - The total amount of drug present in the liquisolid formulation is evaluated using UV spectrophotometric analysis. Approximately weighed quantity of 10mg equivalent of drug is taken from liquisolid formulation which is dissolved in 10ml of methanol and the volume is made upto 100ml with distilled water. From the above solution, 10 ml is taken and diluted with distilled water. The absorbance of resulting solution (10?g/ml) is measured at 234 nm using spectrophotometer (shimadzu UV- 1700 pharma spec, Japan) and the drug content is calculated from the standard curve using the formula

6. Disintegration Time: Wait for a bit for the temperature to reach the required 37⁰C after turning on the device and adding water to the beakers. When the temperature reaches the appropriate level, the alarm will sound on the device. Place each basket case with the six tablets. Press the start button to initiate the disintegration process, and then observe the tablets disappear. Note how long it took for the last tablet to dissolve entirely (no tablet pieces should remain on the mesh covers of the basket).

 Acceptance criteria: Not more than 30 minutes.

7. Dissolution Studies (In Vitro-Drug Release Studies): Using a USP-type 2 (paddle type) device in a sink situation, the model drug release from various formulations was ascertained. The dissolving medium used 900ml of Phosphate buffer of pH 6.8 at 37 ± 0.5°C and 50 rpm. For two hours, the prepared mixture was put through dissolving tests. At predefined intervals (30min,1,2,4,6,8,10, and 12 hours), a 5-milliliter sample was removed, filtered using Whatman filter paper, and replaced with an equivalent volume of dissolving liquid. The UV spectrophotometer was used to measure the amount of drug present in the dissolution sample at 243 nm.
8. Stability studies: The best formulation of three batches is stored at 36° C ± 2°C and relative RH 75% ± 5% for three months. The best formulation is evaluated using dissolution test, drug content, physical appearance, hardness and thickness. The above tests of best formulations are compared with those of freshly prepared tablets. The results showed no significant changes in physical appearance, hardness, thickness, drug content and dissolution test of aged tablets compared to the fresh liquisolid tablets. This indicates that the liquisolid tablets were stable under these storage conditions.

RESULTS AND DISCUSSION

1.Preformulation studies: Pure drug is a white solid that has no odor and slightly bitter taste

2.UV analysis of Teneligliptin: -Absorption maxima (?max) was found to be 243nm

       
           
       
Fig 2: Spectrum of Teneligliptin pure drug

3. Calibration curve of Teneligliptin: -When examined in the range of 200 nm to 400 nm, Teneligliptin showed an absorption maximum [?max] at 243nm. A 0.1N HCL solution was produced with varying concentrations, and the absorbance values at ?-max (243 nm) were recorded. The calibration curves displayed a correlation coefficient of R?2; =0.999

4. Drug Excipient compatibility studies: -The compatibility of pharmacological excipients was investigated using the FTIR spectrophotometer. Teneligliptin and the utilized excipients did not appear to interact, according to FTIR data for both the medicine taken alone and in combination with the excipients.

       
           
       
Fig 4: FTIR Spectrum of Teneligliptin

       
           
       
Fig 5: FTIR Spectrum of Teneligliptin + Propylene glycol

Infrared (IR) spectroscopic studies were carried out to confirm the compatibility between drug and excipients used for the preparation of liquisolid tablets. The IR studies were performed for teneligliptin (pure drug), non-volatile liquid vehicle, microcrystalline cellulose, Aerosil 200 and physical mixture of drug and excipients. The spectra observed at 4000cm-1 to 400 cm-1

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Table 8: - Drug's FTIR compatibility with various excipients

       
           
       
Fig 10: Graph of solubility studies of Teneligliptin

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According to Tables 14,15 and Figure 11, Formulations F1, F4 and F7 were prepared with 1:10, (ratio of drug and Propylene glycol) (ratio of MCC & Aerosil 200) showed the cumulative % of drug release 95.64%, 95.94%, and 93.1% respectively.

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Comparatively Optimized formulation of Teneligliptin made by liquidsolid compact technology showed better drug release than pure drug

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CONCLUSION

In this study, a novel formulation termed as liquid-solid compacts was created by combining API with excipients. Drug excipient compatibility studies verified that Teneligliptin and the other excipients chosen for the formulation were compatible. Precompression factors such as bulk density, tapped density, and Hausner's ratio were assessed for the prepared blend. Following this, post compression parameters such as thickness, hardness, friability, disintegration, and dissolving were assessed for the tablets. After evaluating each formulation, the optimal formulation, identified as formulation F2, was used to load the batch for stability at accelerated stability conditions 36° C ± 2°C and relative RH 75% ± 5% for three months. The formulation passed the evaluations. Thus, it was determined that the formulation's drug release profile was superior. This innovative formulation strategy could be beneficial for increasing bioavailability.

ACKNOWLEDGEMENT
First and foremost, I would like to convey my sincere gratitude and respect for my wonderful mentors, Dr. M. Sunitha Reddy, Principal and Professor, JNTU Sultanpur and Dr. K. Anie Vijetha for proper Guidance and support and the Center for pharmaceutical Science, Institute of Science and Technology, JNTUH. They supported and guided me throughout my research project. They provided some very helpful advice, both conceptually and practically. I sincerely thank them for their contribution.

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