Compatibility studies of the Thiocolchicoside with Eudragit RLPO,Eudragit E100 and Eudragit L100 using thermal and non-thermal methods

Nishant Thakur,Bhupinder Kaur,Manish Goswami,Chandan Sharma

1 University Institute of Pharma Sciences,Chandigarh University,Gharuan,Mohali,Punjab,140413,India.

2 Saraswati College of Pharmacy,Gharuan,Mohali,Punjab,140413,India.

Abstract Aim:Thiocolchicoside is a sulfur derivative of the colchicine widely used as the skeletal muscle relaxant in variety of muscle related disorders.Compatibility of the Thiocolchicoside is screened with the Eudragit RLPO,Eudragit L-100 and Eudragit E-100 for checking its suitability for formulating as transdermal drug delivery system.Methods:The binary mixtures of the drug and polymers were placed in the Petri plates and the temperature and humidity were adjusted at 40 °C ± 2 °C and 75% relative humidity.The drug and polymer mixture were examined on the FTIR and DSC for detection of any possible physical and chemical interactions.Results:Eudragit E100 and L100showed no significant interaction with the Thiocolchicoside and that was justified with differential scanning calorimetry and Fourier transform infrared spectra.However,Eudragit RLPO showed a slight interaction with the drug during the compatibility studies.

Keywords:Thiocolchicoside,Relative humidity,Eudragit,Compatibility,Fourier transform infrared,Differential scanning calorimetry

Introduction

Thiocolchicoside effects the g-amino butyric acids type A receptors and proven to be very effective as skeletal muscle relaxant,anti-inflammatory,and analgesic effects the central nervous systems and provides a relief in the muscle pain [1,2].Conventional topical formulations provided the adequate spreading and contact with the affected area on the epidermis and hence to avoid the direct contact and deliver the medication into the affected area were developed with various polymers increasing the patient compliance [3] esters of acrylic and methacrylic acid,popularly known as the Eudragit whose properties depends on the functional group attached,Eudragit is available in the various forms [4] Eudragit is biocompatible and capacity to load the drugs and,adhesive in nature and have considerable swelling index.These polymers can be formulated easily into reservoir or matrix systems [5].These polymers are pH sensitive and like Eudragit E100 and L100 and commonly used as enteric coated polymers.Eudragit L100 dissolves in the pH 5.5 to 6.0 and can be used to deliver the medication to ileum,while S100 can provide the release in the pH range of the 7.0 and hence deliver the medication the in the large intestine [6].These polymers need to be investigated for the drug polymers interaction to optimize the release and stability.Number of physiochemical methods are used for the determination of the compatibility include the differential scanning calorimetry (DSC)and Fourier transform infrared (FTIR) [7].When compared to other methods FTIR provides capability to detect the changes in the crystal structure,degree of hydration and other polymeric changes [8].Eudragit has also been found to provide the site-specific release and used in the coating of the granules and transdermal systems with the Pentazocine has also been developed with the Eudragit.

Materials and methods

Materials

Thiocolchicoside was procured from Yarrow Chem Mumbai.Eudragit RLPO,Eudragit E100 and Eudragit L100 was also purchased from Yarrow chem India ltd.All the chemicals used in the study were of analytical grade.IR spectrophotometry was carried out on the Perkin Elmer spectrum two (UATR TWO) and DSC was performed on the Q-10,TA Instruments Waters at GJUST Hissar,Haryana India.

Methodology

Drug and polymers were weighed in the equal ratio (1:1) and placed in the glass Petri plates.An initial identification was done on the basis of the FTIR and DSC [8,9].Glass petri plates were stored in the humidity chamber.The temperature and humidity were adjusted at 40℃ ± 2 ℃ and 75% relative humidity (RH).The drug and polymer mixture were examined on the FTIR and DSC for detection of any possible physical and chemical interactions (Figure 1) [10,11].

Results and discussions

FTIR spectroscopy can be used to explore the molecular arrangements with crystalline arrangement and planar hydrogen bonding for different solid-state forms.Characteristic carbonyl group (NH2) band at 1525.42 cm-1,C=O structure (tropane ring) at 1663.64 cm-1,Amide II band (N-H str) at 3325.9 cm-1,thio-ether band at 2360.7 cm-1and OH group stretching band at 3493.2 cm-1were found for Thiocolchicoside.Form I of Thiocolchicoside showed characteristic carbonyl group band at 1558.3 cm-1,C=O (tropane ring) at 1654.8 cm-1,Amide II band (N-H str) at 3247.9 cm-1,thio-ether band at 2360.1 cm-1and hydroxyl group stretching band at 3400.2 cm-1and free -OH stretching band at 3545.7 cm-1(Figure 2,Table 1) [12,13].Esterified groups were present at 1150-1190 cm-1,1240 cm-1and 1270 cm-1while carbonyl at 1730 cm-1[14].Hydrocarbon chain vibrations were found at 1385 cm-1,1450-1490 cm-1and 2950 cm-1.DMAE groups were observed at 2770 cm-1and 2820 cm-1and RNH stretching signal at 3435 cm-1due to protonated ammonium salt (Figure 3,Table 1) [15].

The spectra of Eudragit L-100 show the carbonyl vibrations of the ester group at around 1728 cm-1.The Eudragit L100 OH (3170 cm-1),CH Stretching Aromatic (3067 cm-1),CH Stretching Aliphatic (2954 cm-1),C=O (1598 cm-1),Aliphatic-CH-bend (1672 cm-1),Aromatic-CH in plane bending (1134 cm-1) (Figure 4,Table 1) [16].

Tertiary amine was present at 1731.4 cm-1and 3432.1 cm-1due to presence of the C=O bond for Eudragit RLPO and a peak was observed at 1450.2 cm-1for CH3bend (Figure 5,Table 1) [17].

Figure 6 Thiocolchicoside and Eudragit-RLPO IR Spectra

Figure 7 Drug and Eudragit E100 IR Spectra

Figure 8 Thiocolchicoside and Eudragit L100 IR Spectra

Figure 9 Overlay patterns of Thiocolchicoside,Eudragit E100,Eudragit L100 and Eudragit RLPO in Essential FTIR

Figure 10 DSC thermogram for the Physical mixture of the Eudragit E100,L-100 and Eudragit RLPO

Table 1 :IR spectra of compounds and their elaboration

Figure 1 Graphical abstract

Figure 2 Thiocolchicoside IR Spectra

Figure 3 Eudragit E100 IR Spectra

Figure 4 Eudragit L-100 IR Spectra

Figure 5 Eudragit RLPO IR Spectra

Thiocolchicoside and polymer interaction’s study

Thiocolchicoside exhibit the characteristic finger print identification peaks at 1525 cm-1,1663 cm-1and 2360 cm-1.These peaks are due to the amide groups ether groups and C=C groups.These identification peaks and the fingerprints can be observed with all the characteristic interaction spectra.However,the polymers also exhibit their characteristics peaks and indicates no sign of the interaction (Figure 6).Eudragit E100 was able to maintain its characteristic peaks for C=O stretching and was detected at 1712 cm-1along with the identification peaks of Thiocolchicoside at 1644 cm-1,1517 cm-1and 1720 cm-1(Figure 7) [18].The physical mixture of the Eudragit L-100 with Thiocolchicoside maintained all its identification peaks in the fingerprint regions.The main peaks of the Eudragit L-100 were identified at 1709 cm-1,2998 cm-1,3067 cm-1,2951 cm-1,1156 cm-1.After a one-month interaction study the finger print regions for Eudragit L-100 were identified at 1156.86 cm-1,1253.37 cm-1,1712.30 cm-1along with the Thiocolchicoside 1156.83 cm-1,1074 cm-1and 1479 cm-1(Figure 8) [15].The identification peaks were easy to identify and hence no interaction can be visualized in the case of the Thiocolchicoside and Eudragit E100.In the IR spectra of the drug and Eudragit RLPO a shift in the tertiary amine group to 3424 FTIR spectrum of Eudragit RLPO showed the peak at 3432.1 cm-1due to the presence of tertiary amine,at 1731.4 cm-1due to the presence of C=O(ester),and at 1450.2 cm-1due to -CH3 bend.The spectrum of PVP K30 showed important bands at 2955 cm-1(C-H stretch) and 1655 cm-1(C=O).A very broad band was also visible at 3425 cm-1was observed as the widening of the peak.Stretching in the C=O group in the ester was found indicating the hygroscopic nature of the polymer.The amide group and ester group are prone to hydrolysis and indicates the possibility of the polymer to interact with the moisture and polar solvents.Thiocolchicoside fingerprint regions did not deviated much in the spectra showed their presence at the 1349 cm-1,1663 cm-1,1602 and 1237 cm-1[19,20].

The amine and ester groups are prone to the action of the water and a widening in the spectra was observed.It can be concluded that the physical mixtures are not at much risk for any sort of the interaction,however a solvent and processing conditions should be adjusted while working with the Eudragit RLPO [21].We have postulated that presence of the water in the mixture can form the lumps and result in the decrease in the activity and consistency of the mixture in the transdermal drug delivery system.

The overlay spectra of the drug and polymers was also studied on the software essential FTIR v3.50 trial version and the fingerprint regions were overlapped with the spectra of the drug to identify any dissimilarity and data for the peak pick was observed (Figure 9).

Determination of the physical purity by Differential scanning calorimetry

Eudragit L100 and Eudragit S100 showed broad endotherms with peaks at 216.2 °C and 188.51 °C respectively which are typical for amorphous material.Glass transition temperature of Eudragit RLPO is at 70 °C (Figure 10).Drug showed glass transition temperature between 105-115 ℃ and a sharp exothermic peak at the 128 ℃leading to endothermic peak at the 198 ℃ with highest enthalpy 65.979 J/g leading of the melting of the compound (Figure 11) [22].

Figure 11 DSC Thermogram of Thiocolchicoside

Conclusion

The drug polymer compatibility study between the Thiocolchicoside and Eudragit E100,Eudragit RLPO and Eudragit L100 was carried and interpreted by studying IR spectra,DSC thermogram.Eudragit E100 and Eudragit L100 are more stable as compared Eudragit RLPO.Eudragit RLPO was postulated to be prone for hydrolysis and possible degradation in the presence of the water.Eudragit polymers were found suitable for formulating a transdermal drug delivery system.

Summary

Thiocolchicoside is a strong muscle relaxant.Binary mixtures of the Thiocolchicoside and Eudragit polymers were tested for compatibility under the stressed conditions 40 ℃ ± 2 ℃ and 75% RH.The binary mixtures were analyzed by DSC and IR spectroscopy for any possible interaction.All the fingerprint regions of the drug and polymer were identified and it was deduced that Thiocolchicoside shows no interaction with the Eudragit E100 Eudragit L100.While the IR spectra of the mixture containing the drug and Eudragit RLPO showed its susceptibility for degradation in the hygroscopic environment.