Physico-Chemical Characterization of Paliperidone Palmitate and Compatibility Studies with its Pharmaceutical Excipients

Aim: The main aim of the present study was to characterize and perform the compatibility studies of paliperidone with its excipients. Study Design: Physico-chemical characterization and compatibility studies. Place and Duration of the Study: Chalapathi Drug Testing Laboratory, Chalapathi Institute of Pharmaceutical Sciences, Chalapathi Nagar, Lam, Guntur-522034 between December 2020 and January 2021. Methodology: Physico-chemical characterization and compatibility studies of paliperidone palmitate with its excipients like HPMC, lactose, magnesium stearate, talc, microcrystalline cellulose was done using the FTIR spectrophotometer, Scanning electron microscopy, X-ray diffraction, Differential scanning calorimeter. Results: Interaction of the paliperidone palmitate with its excipients were studied by this technique. Paliperidone palmitate showed the transition at 117.92C with the specific heat of 101.9J/g. The IR Original Research Article Nadendla et al.; JPRI, 33(5): 85-91, 2021; Article no.JPRI.66153 86 spectrum of paliperidone palmitate and excipients mixture has shown a characteristic stronger band of the N-H at 3412.75cm, C-H at 2921.98 cm, stretching vibrations of C=O at 1737.47 cm, C=C at 1651.94 cm, N-O at 1541.16 cm followed by C-F at 1160.46 cm. XRD showed good crystalline properties with relative crystallinity index of 60.01%. The photomicrographs obtained by SEM did not evidence any interaction between paliperidone palmitate and the excipients, providing visual support for the results. Conclusion: There were no interactions of drug with selected excipients and found to be compatible. Therefore, it is a mandatory clause for the compound compatibility with various excipients in the formulation which affect the stability and efficacy of the formulation.

spectrum of paliperidone palmitate and excipients mixture has shown a characteristic stronger band of the N-H at 3412.75cm -1 , C-H at 2921.98 cm -1 , stretching vibrations of C=O at 1737.47 cm -1 , C=C at 1651.94 cm -1 , N-O at 1541.16 cm -1 followed by C-F at 1160.46 cm -1 . XRD showed good crystalline properties with relative crystallinity index of 60.01%. The photomicrographs obtained by SEM did not evidence any interaction between paliperidone palmitate and the excipients, providing visual support for the results. Conclusion: There were no interactions of drug with selected excipients and found to be compatible. Therefore, it is a mandatory clause for the compound compatibility with various excipients in the formulation which affect the stability and efficacy of the formulation.

INTRODUCTION
Paliperidone palmitate Fig. 1  Thermal techniques are used for analysis of pharmaceuticals and excipients. Different techniques include differential scanning calorimetry (DSC), differential thermal analysis (DTA) and crystallographic technique like X-ray diffraction and scanning electron micros copy (SEM) in which substances are analysed based on their physical properties reactions with the temperature and are measured by temperature difference [3][4][5].
Drug-excipient compatibility studies during the formulation development is a significant process in getting to know about the physical and chemical interaction between the substance and excipients [6][7][8]. This process of knowing the in compatibility, by comparing the thermal curves of substance with pharmaceutical excipients used in formulation in the ratio of 1:1 for their evaluation. Infrared spectrophotometer is used for the characterization of the compounds and excipients [9][10][11]. It is done based on the analysis of functional groups present in the compound and in excipients. XRD was used in knowing the crystal structure and properties of the molecule and also lattices in the molecule, whereas SEM was used to identify problems with particle size and shape of the molecule [12,13].

Materials
Paliperidone palmitate bulk material was procured from Merck. The tested pharmaceutical excipients were procured from local vendor national scientific products.

Instrument
Differential scanning calorimeter manufactured by TA instruments of Q20 model was used for the studies by using TA instrument explorer and TA universal analysis software's under nitrogen atmosphere with the flow rate of 10 mL/min. Approximately 2 mg of samples were weighed and sealed in the aluminium pans. The temperature program was given from 30 to 300°C at a heating rate of 10°C/min. Infrared spectrophotometer manufactured by Bruker of Alpha model was used for the characterization of compounds using OPUS software.

Preparation of Physical Mixtures
The study for the interactions was performed by using a physical mixture of paliperidone palmitate and excipients of equal proportions (1:1 W/W). The mixtures were prepared in the way of simple mixing using the motor and pestle, weighed of required quantity and were sealed in the aluminium pans for the analysis.

Characterization and Compatibility Studies
The DSC curve obtained for paliperidone palmitate are shown in Fig. 2. The DSC curve has shown a sharp endothermic curve at (T Peak =117 0 C; T Onset =116 0 C; DH Fusion =101.9Jg -1 ), corresponding to melting point followed by decomposition. The DSC data allow evidencing a thermal stability upto 180°C. Also small broad exothermic peak was seen from 210-260 0 C which indicates the oxidation and followed by decomposition from 260°C.
The IR spectrum of paliperidone palmitate has shown in Fig. 3 In fact, DSC has been proposed to be a rapid method for evaluating physic chemical interactions between components of the formulation through the comparison of thermal curves of pure substances with the curve obtained from a 1:1 physical mixture and therefore select adequate excipients with suitable compatibility.
DSC curve of paliperidone palmitate / HPMC / lactose / magnesium stearate / talc/ microcrystalline cellulose has shown in Fig. 4 as an endothermic event of melting point of paliperidone palmitate in the range of 147-151 0 C, followed by melting point at 116.40°C. Finally, the result showed that the absence of movement of the melting drug transition suggests there were no covalent or other strong interactions with that of its excipients. Hence it is was compatible with that of its excipients.
IR spectroscopic studies has been applied as a supplementary technique to investigate drug excipient interaction and to conform the results obtained from the thermal analysis [14,15]. It is the most suitable technique of nondestructive spectroscopic methods and has become an attractive method in the analysis of pharmaceutical solids, since the materials are not subject to thermal or mechanical energy during sample preparation, therefore preventing solid state transformations [11,3]. The appearance of new absorption bands, broadening of bands and alteration in intensity is the main characteristics to evidence interactions between drug and excipients.
The spectra of the drug and all excipients used in this study were obtained for pure compounds as well as binary mixtures (1:1 mass/mass) in order to identify a possible chemical interaction between them.
The IR spectrum of paliperidone palmitate and excipients mixture was shown in Fig. 5 with a characteristic stronger band of the N-H at 3392.85cm -1 , stretching vibrations of C-H at 2920.31 cm -1 , C=O at 1737.37 cm -1 , C=C at 1652.18cm -1 , and C-F at 1021.37 cm -1 . Moreover, the spectra of binary mixtures can be considered as the superposition of the individual ones without absence, shift or broadening in the vibration bands of paliperidone palmitate. X-ray powder diffraction has been used for qualitative and quantitative identification of crystallinity. The XRPD patterns of paliperidone palmitate revealed several diffraction peaks which indicate its crystalline character was shown in Fig. 6. The relative crystallinity of paliperidone palmitate was calculated based on the Ruland method, in which the area of the crystalline diffraction relative to the total area of the diffractogram is taken as a measure of crystallinity. The relative crystallinity index calculated for paliperidone palmitate was 60.01%.
The SEM photomicrographs taken at magnification 500 and 7000 are given in Fig. 7. It was observed that paliperidone palmitate is characterized by regular shaped crystals. The photomicrographs obtained by SEM did not evidence any interaction between paliperidone palmitate and the excipients, providing visual support for the results. The SEM images have shown that both paliperidone palmitate and excipients particles maintained their morphology and the drug crystals appeared dispersed on the surface of excipient particles.

CONCLUSION
The thermal analysis provided information about the thermal stability and decomposition of pure paliperidone palmitate and the binary mixtures which can be used in the quality control. The characterization was obtained by IR and DSC, which, in turn, demonstrated paliperidone palmitate physicochemical properties including the crystallinity. In the compatibility studies, the modifications found in the DSC curves suggested that there was no possible physical interaction of paliperidone palmitate with magnesium stearate, starch and micro crystalline cellulose. Additional IR analysis were carried out and no evidence of solid-state interaction or incompatibility was observed. XRD of paliperidone palmitate indicated that the compound is crystalline in nature with good diffraction properties. SEM was carried out with paliperidone palmitate with its excipients and results showed that there were no interactions with good crystal properties from SEM photomicrographs.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.