Preparation and Characterization of Temozolomide Matrix Tablets UsingDatura stramonium Leave Mucilage for the Treatment of Brain Cancer

INTRODUCTION

The cancer isthreatening every living being on the globe, when the cancer-related to the brain is more pathetic. An appreciable work has done to diagnose, and treatment of cancer, butthe mortality rate threatens all.¹

Temozolomide (TZD) is an oral alkylating agent to tackle brain cancers and to handle glioblastoma multiform and astrocytoma. TZD is about theimidazotetrazine group, with cent percent bioavailability with a mean half-life of 1.2h and good drug in the present study.²

Prolonged drug delivery systems with zero-order drug release can be achieved by various techniques, among them matrix system is simple, economical and effective.³ The use of costly polymers can be replaced by the economical and easily available weed herb- Datura stramonium leaves mucilage (DSLM).

MATERIALS AND METHODS

MATERIAL

The materials required in this work are illustrated in table 1.

METHODS

Identification of Temozolomide

Identification of TZD was scrutinized for a physical look, melting point and solubility.

Method to estimate Temozolomide

TZD was dissolved in phosphate buffer pH 2.0 obtain 10 μg/ml solutions. Further diluted with the same buffer and scanned for λmax in a double beam UV-VIS Spectrophotometer, at 200 to 400 nm and λ max was found to be 330 nm4.

Temozolomide calibration curve

The procedure for plotting the TZD calibration curve⁵ was illustrated in chart 1.

Extraction of mucilage

The extraction and purification were performed as styled by Ahadet al.,2012⁶. The fresh Datura stramonium leaves were washed, soaked and boiled in water. Later filtered isolates with Acetone,dried, # 80 sieved.

Drug excipient compatibility studies

Differential scanning calorimetry (DSC)

The DSC analyses of the TZD and formulations blend were achieved with Perkin Elmer, FTIR spectrophotometer to check any drug-excipient interaction. Each sample was placed in an aluminium pan separately with heating rates of 10°C/min from 50-300°C under nitrogen 50 ml/ min.

FTIR study

FTIR spectra and characteristic peaks of TZD and TZD with an excipient blend were made by Bruker IR spectrophotometer.

Calibration curve

The TZD calibration curve shows a slope of 0.057x+0.0545 with a regression (R2) value of 0.9991 (Fig 1.).

Formulation of tablets by wet granulation technique

Steps involved in the preparation⁷ of MT shown in chart 2.

Pre formulation studies

The granules were subjected to flow patterns for checking their easy movement from the hopper to the tablet dyes for compression.^8,9

Post formulation studies

The prepared tablets were characterized for the following parameters.^10,11,12

Thickness of tablets

A sliding caliper was used to know the thickness of 5 tablets from each batch.

Uniformity of weight

20 tablets from each batch were weighed solely, and the mean weight was resolute. Later the unorthodoxy of individual weights was calculated.

Tablet hardness

5 tablets were randomly taken from each batch, and hardness was dogged by using Pfizer tester.

The loss on friability

A pre-weighed 10 tablets from each batch were allowed for 100 falls (4 min) from 6 inches and weighed after removing the dust.

Determination of drug content in tablets

TZD content in the MT was dogged by the procedure explained in chart 3.

In vitro dissolution studies

The dissolution conditions adopted for drug dissolution were concise in table 2.

RESULTS AND DISCUSSION

Results API characterization

TZD appearance, melting point, and solubility were listed in chart 4.

Compatibility studies

Neither loss of specific peaks nor emissions of new peaks was seen in the DSC of TZD thermogram when compared to pure TZD which indicates no incompatibility of TZD with polymers used (table 3).

The FTIR spectra expressed that the typical bands of TZD were not rehabilitated in the physical mixtures, which confirms no negative dealings between TZD and EC and DS polymers.

Pre formulation studies

The flow parameters of the granules were illustrated in table 4.

Post formulation studies

The prepared MT was found to have uniformity in thickness (5 mm) and weight which represents the drug and excipients were blended systematically. The loss on friability was negligible (1%) and the hardness was > 4 Kg/cm2 indicates that the MT has appreciable strength. The TZD content in MT was found to be satisfactory as per the specifications (Table 5). The in vitro release indicates the controlled release of TZD from the formulation. Among the formulations, MT-5 showed controlled release for a prolonged period(Fig.2).

Release kinetics and mechanism

To know the mechanism of releaseand the kinetics of TZD optimized formulation, MT-5 fit into mathematical models and the R2 values for zeroorder, first order, Hixson Crowell’s and Korsmeyer Peppas models were illustrated in Table 6. This study revealed that the TZD release from the devices followed non-fickian release as the ‘n’ value is >0.5.

CONCLUSION

The authors in this study observed that the Temozolomide matrix tablet, extended the emission rate for a prolonged duration of more than 12 h with increased bioavailability and devoid of repetitive dosing and dose. This was also noted that Datura stramonium leaves mucilage can be a good polymer in combination with Ethylcellulose for controlling the drug release with reduced adverse effects and cost and with improved patient happiness and effectiveness.