INTRODUCTION:

The production of pharmaceutical formulations necessitates prior knowledge of drug and excipient physicochemical properties. Excipients are known to assist in the administration and modulation of active ingredients; they are considered pharmaceutically inert, while chemical and physical associations with active compounds are probable¹. The foundation for choosing the best excipients and designing a chemically stable and efficient dosage type is laid by medication compatibility studies^2,3. Excipient selection is assisted by early stages of drug compatibility testing, which enhances the possibility of delivering a safe dosage type⁴. Despite the importance of the problem, there is no generally accepted method for testing drug-excipient incompatibility^5,6.

The preformulation stage for the design and development of any novel formulation will include the evaluation of drug-excipient compatibility employing various methods along with thermal and isothermal stress testing.

Differential Mode Scanning Calorimetry is a common thermal technique for determining the functionality of drug excipients. However, deciphering thermal data isn't always easy, and it's important to remember that association’s exposure to high temperatures may or may not be true under normal conditions^7,8.

As a result, experimental techniques such as Fourier Transform Infrared (FTIR) Tomography, which is focused on the assumption that the same component shifts during drug-excipient interactions^9,10 are used in compatibility studies.

The aim of this study was to determine the consistency of Lamotrigine with various drug formulations to be used in novel formulations using various testing procedures such as differential scanning calorimetry and Fourier Transform Infrared Mass spectrometry.

MATERIAL AND METHODS:

Swarnoop Chemicals Pvt. Ltd. in India supplied the lamotrigine. Sigma Aldrich in India given the sodium alginate and Chitosan. The rest of the chemicals and reagents were of analytical quality.

Identity Examinations:

Physical Features:

Swarnoop Chemical Pvt. Ltd, Pune, provided the drug (Lamotrigine) as a gift sample. Lamotrigine was supplied as a white amorphous odourless powder.

Melting point:

Melting point apparatus (Tempo, Mumbai) was used to calculate the melting point of Lamotrigine, which was found to be 217.2°C¹¹.

Solubility:

The sample's absorption in different solvents was measured qualitatively. It was measured by shaking 10 mg of drug sample in 10ml of solvent (e.g., Water, 0.1M Hydrochloric acid, Methanol, Ethanol, Dimethyl Sufoxide (DMSO), Chloroform, Phosphate Buffer Saline -pH 7.4) in tiny test tubes and recording the time it took to completely dissolve the sample. Solubility profile of Lamotrigine is recorded in Table 1¹².

Table 1: Solubility profile of lamotrigine

S. No	Solvent	Solubility	Concentration in mg/mL at 25ºC
1	Water	Insoluble	0.15
2	Phosphate Buffer Saline -ph 7.4	Sparingly soluble	2.4
3	0.1M hydrochloric acid	Sparingly soluble	4.3
4	Methanol	Sparingly soluble	1.2
5	Ethanol	Soluble	6.2
6	DMSO	Soluble	6.6
7	Chloroform	Sparingly soluble	3.2

Determination of λ_max:

In a 100ml volumetric flask, 10mg of Lamotrigine was accurately measured and dissolve in 100ml of ethanol. Then 1mL of the stock was pipetted into 10mL volumetric flask, or with distilled water, the equilibrium was brought up to the desired level. A Shimadzu UV-visible spectrophotometer was used to scan the resulting solution between 200 and 400nm. The λmax was found to be 229.6nm as shown in Fig.1)¹³.

Fig 1: λ_max of Lamotrigine

Differential Scanning Calorimetry (DSC):

In a DSC aluminium tray, different specimens (drug and excipients) and also a solid dispersion of drug substances were weighed to around 5mg. The sample pan was crimped and screened in the 50-300°C temperature range for effective heat transfer. The thermogram was checked for proof of any interactions at a temperature of 20°C min^-114,15.

FT-IR:

Fourier Transform Infrared spectra were recorded in the frequency band 400- 4000cm^-1 with the a frequency of 4 cm-1 using the potassium bromide discs system on a Spectral analysis using the instrument Bruler FT-IR. The drug and each of the specified active ingredients (1:1w/w) were held at 402^oC and 75percent RH for 30 days. Lamotrigine, individual excipients, and combinations of medicine and excipients were crushed, thoroughly combined with potassium bromide in a mortar for 3-5 minutes, and compressed into discs for 5 minutes using a hydraulic press at a pressure of 5 tonnes. The sample concentration in potassium bromide must be between 0.2 percent and 1 percent. The pellets are put in the direction of the light, and the spectrum were collected and analysed for any signs of interactions.^16,17.

Preparation of lomotrigine nanoparticles:

Ionotropic pregelation method:

Rajaonarivony's alginate–poly-Lysine NP preparation method was adapted into a two-step procedure. To begin, different concentrations of chitosan (CS), sodium alginate (ALG), and CaCl₂ are acquired, CS is diluted in 1percent acetic acid, then pH is adjusted to 5.5 by NaOH; ALG is diluted in distilled water, then pH is prepared to 5.0–5.3 using HCl; and at neutral pH, CaCl₂ is diluted in distilled water. The calcium alginate pregel is made using combining 6mL of aqueous CaCl₂ solution (0.5, 0.75, and 1 percent) with 10ml ALG solutions (0.2, 0.4, and 0.6 percent) comprising 5mg/ml of LTG for 30 minutes at 400rpm while stirring. In the second step, 4mL of CS solution (0.1, 0.2, or 0.3percent) is applied to the calcium alginate pregel and stirred continuously for next thirty minutes. And make it possible for temperature to shape^18,19.

SEM studies:

Scanning Electron Microscopy analysis of the prepared formulations is carried out to understand the morphology of nanoparticles. Using a sputter coater, nanoparticles should be fixed on aluminium studs and gold-coated. The samples will be sputter-coated three times (2 minutes) at a current pressure of 20mA under vacuum (0.1mmHg). The morphology of drug-loaded nanomaterials will be examined using transmission electron microscopy²⁰.

RESULTS AND DISCUSSION:

Differential scanning calorimetry:

Figures 2 to 7 show the DSC thermograms for lamotrigine, chitosan, sodium alginate, and complexes such as lamotrigine with sodium alginate, lamotrigine with chitosan, and a combination of lamotrigine with all excipients. The melting point of lamotrigine is 219.79°C, Figure 2 show a wide endothermic band for formulation with chitosan and sodium alginate, which was linked to water molecule loss, i.e. the dehydration process. As a consequence, there is no interaction between lamotrigine, sodium alginate, and chitosan. The medicine had such a high sharp endothermic at 220.23°C on the thermogram, which corresponded to the melting. As a result, the drug's boiling endotherm shifted from 219.79 to 220.23°C, indicating that the medicine and active ingredients were mixed, decreasing the clarity of each part of the drug-mixture. Lamotrigine, sodium alginate, and chitosan had no interaction according to the findings.

Fourier transform infrared spectroscopy (FT-IR):

The FTIR method can be used to evaluate the implications of different functional groups of guest and host molecules by analyzing significant changes in the shape and position of the absorbance bands. In Figure 3, the infrared spectrum of chitosan can be seen. A wide band in the 3448–3382 cm^-1 range represents N-H and O-H stretching, as well as intramolecular hydrogen bonds. The absorption bands at 2921 and 2877 cm^-1 are caused by C-H symmetric and asymmetric stretching, respectively. These bands are polysaccharide-specific and can be found in the spectra of other polysaccharides. The presence of residual N-acetyl groups was confirmed by bands at about 1662 cm^-1 (C=O stretching of amide I) and 1379 cm^-1 (C-N stretching of amide III). We find a small band at 1550 cm^-1 that corresponds to N-H bending of amide II. The third band found in N-acetyl groups will be this one. The primary amine's N-H bending is characterized by a band at 1585 cm^-1. The presence of bands at 1421 and 1379 cm^-1 confirmed the CH2 bending and CH₃ symmetrical deformations, respectively. The absorption band at 1155 cm^-1 is caused by the irregular stretching of the C-O-C Bridge. The bands at 1074 and 1029 cm^-1 characterize C-O stretching. All of the bands were discovered in the spectra of chitosan samples taken by others. The stretching vibrations of asymmetric and symmetric bands of carboxylate anions are due to the absorption bands about 1606 cm^-1, 1421 cm^-1, and 1319 cm^-1, respectively, in this figure. The peak at 3234-3483 cm^-1 corresponds to hydroxyl group stretching vibrations. Stretching vibrations C-H symmetric and asymmetric stretching have a frequency of 2935 cm^-1. The presence of high absorption bands at 3450/cm, 3315/cm, and 3267/cm, 3213/cm, all of which are representative of amines, characterises the spectrum of lamotrigine (-NH- group).

At 1620/cm (C=O stretching) and 792/cm, the carbonyl-stretching mounts as a very powerful doublet, suggesting the presence of aromatic rings. This means that polymers and in formulation have no effect of lamotrigine.

Fig. 2: DSC thermogram of Lamotrigine + Chitosan + Sodium Alginate

Fig. 3: It shows FTIR spectrum of lamotrigine + Chitosan + Sodium alginate (1:0.5:0.5)

Fig. 4: SEM Morphological Studies

In this research, imaging spectroscopy (SEM) was used to analyse the morphology of the nanoparticles (Figure 14). The formation of spherical nanocomposite nanomaterials with a flat surface and no surface fracturing or pitting was revealed by SEM photos.

CONCLUSION:

The interaction of Lamotrigine with various excipients such as chitosan, sodium alginate, and mixture was investigated through specific methodologies like differential scanning and Fourier Transform Infrared Spectroscopy. Techniques like FTIR and isothermal stress testing can be used in conjunction with DSC data to draw any definitive conclusions after storing Lamotrigine and individual excipients in stressed conditions. In this analysis, the findings of DSC and FTIR were used to successfully determine the protection of Lamotrigine with the excipients. There was no evidence linking Lamotrigine to excipients such as Chitosan or sodium alginate. During the two weeks of storage at 50°C, there was no noticeable colour shift. As a result, this knowledge supports the excipients' ability to efficiently produce the nanoparticle formulation.

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Received on 09.04.2021 Modified on 21.08.2021

Research J. Pharm. and Tech. 2022; 15(8):3443-3446.

DOI: 10.52711/0974-360X.2022.00576