Pharmaceutics: Drug Excipients Compatibility Analysis by Fourier Transform Infrared Spectroscopy - Term Paper Example

Pharmaceutics: Drug Excipients Compatibility Study Report by FTIR Name Institution Intstructor Course Date of Submission Introduction Fourier Transform Infrared spectroscopy (FT-IR) is one of the experimental techniques that can be used to optimize and analyze drug-excipients compatibility. This study aims to investigate the compatibility and interaction between Metoclopramide and some excipients/polymers. This paper reviews FT-IR as one of the spectroscopic approaches in the pre-formulation of Metoclopramide to determine its drug-excipients compatibility properties. This method is cost effective, minimizes wastage, and saves time. Compatibility studies provide a basis for choosing the best excipients for drug formulations. Methodology Samples comprising of several buccal films were prepared. Each film composed of Metoclopramide HCl, 1 or 2 polymers, Saccharine, Flavor, and Glycerol in aqueous media. Potassium bromide (KBr) pellet technique was used to prepare the solid samples for IR analysis. The drug excipients compatibility study was performed using the Nicolet iSTM 10 FT-IR Spectrometer. This machine uses the KBr or Ge mid-infrared standard beam splitter. The spectral range is 400-7500 cm-1 (wave numbers). The experimentation used pure powdered drug and selected excipients (Chitosan, Sodium Carboxymethyl Cellulose [CMC], Gelatin, Flavor, Hydroxyethyl cellulose [HEC], Glycerol, hydroxypropyl methylcellulose [HPMC], Hydroxypropyl cellulose [HPC], Na Alginate, Metoclopramide, and NA Saccharine) as well as films (A1 – A23) with their polymeric composition. The polymer was mixed with the drug in which composition, flavor, glycerol, and saccharine were added. The mixture was prepared until transparent pellets formed. While utilizing KBr disks, which were in dry and powdery state, the disks were put in the spectrophotometer for recording of the spectra. The infrared spectra were tapped by the Nicolet iSTM 10 FT-IR Spectrometer whose spectral range is 400 – 7500cm-1. A single beam with absorption bands from each of the samples is then collected and assigned to appropriate modes of vibrations during analysis. The physical parameters detected by the machine generate an interferogram, which is changed to an IR absorption band, which is identified with a plot of % Transmittance versus the Wave-numbers (wavelength). The ratio of beaming power put out by a sample (I) with respect to the beaming power of incident rays on the sample (I0) leads to transmittance (T). Thus, Absorbance (A) is given by: A = log101/T = -log 10T Utilization of FT-IR can be used to analyze the structure of molecules as well as generate comparisons in the spectra of the drug and excipients. Results A1 (2% Na Alginate) In the film with 2% Na Alginate, the highest transmittance achieved was 90%T 2900 cm-1 (wavelength) while the lowest transmittance achieved was 50%T at a wavelength of 497 cm-1. A3 (1% Na Alginate + 1% Na CMC) In the film labeled A3, the highest transmittance achieved was 99%T 3000 cm-1 (wavelength) while the lowest transmittance achieved was 88%T at a wavelength of 550 cm-1 A6 (2% Na CMC) In the film labeled A6, the spectroscopy started at transmittance of 102% and wavelength of 3700 cm-1. The sample recorded a peak at 93%T (3000cm-1) and the lowest transmittance achieved was 47%T at a wavelength of 466 cm-1 A7 (2% Na CMC + 1% HEC) The film labeled A7 had the highest transmittance of 93% at 3000 after an initial start of 102%T at 3700. The lowest transmittance reached was 42%T at 1020cm-1 while the lowest wavelength reached was 469cm-1. A8 (1% Na CMC + 1% HPMC) This analysis recorded a peak at 86%T (3020cm-1) and faded off at 48%T (557cm-1) A10 (1% HPMC) Film A10 started at 100%T (3700cm-1) and attained a high transmittance of 86% at 3020 and a low transmittance of 44% at 1010cm-1. A11 (1% HEC + 1% HPMC) + drug, saccharine, flavor and glycerol Started at 99%T and 3700cm-1 reached a peak transmittance of 99% and peak wavelength of 3350cm-1 with the lowest transmittance of 43% and wave-numbers of 442.4cm-1. A12 (1% Chitosan: 4% Gelatin (1:1) Transmittance of 75% at 3250cm-1 that rose to 90%T at 3010cm-1. The lowest transmittance recorded was 45%T at 520cm-1 whereas the lowest wave-number recorded was 414cm-1 at 63%T. A13 (1% Chitosan: 4% Gelatin (2:1) Film A13 started at transmittance of 99% at 3700cm-1. This rose to a peak of 103%T at 3000cm-1. The lowest transmittance recorded was 43%T at 320cm-1. A14 (1.5% Chitosan: 1% HEC (4:1) In the film labeled A14, the highest transmittance achieved was 100%T of 2400 cm-1 after starting at 103%T. Whereas the lowest transmittance achieved was 51%T at a wavelength of 1010 cm-1 A15 (1% Chitosan) In the film labeled A15, the spectroscopy started at transmittance of 100% and wavelength of 3700 cm-1, rose to a peak of 105% (2950cm-1) and attained a low transmittance at 61%T at a wavelength of 510 cm-1. A18 (1% HPC + 1% Na Alginate) In the film labeled A15, the spectroscopy attained a peak of 105% (2950cm-1) and attained a low transmittance at 51%T at a wavelength of 510 cm-1. A19 (1% HPC + 1% Na CMC) Spectroscopy of A19 attained a peak of 99% (1750cm-1) and attained a low transmittance at 44%T and a low wavelength of 416 cm-1. A21 (1% HPC + 1% HPMC) Spectroscopy of A19 attained a peak of 106% at 2950cm-1 and a low transmittance at 50%T and a low wavelength of 437 cm-1. A23 (1% Na CMC + 1% HEC) The film, A23 started at a transmittance of 99% and the spectroscopy attained a peak of 104%T at 2950cm-1 and a low transmittance at 31%T and a low wavelength of 460 cm-1. Chitosan Transmittance achieved two peaks. One at 117%T (460cm-1) and the other one at 142% (420cm-1). This recording is typical of the active ingredient. CMC A peak at 123%T and waveunumber3250cm-1 was recorded. This was followed by another peak at 113%T (2940cm-1). Another exponential increase in transmittance was recorded at 155%T of 1010cm-1. Presence of several peaks at different levels may suggest incompatibility with API. Flavor Several peaks were recorded. One of them was at 122%T while the other sharp peak was at 144%T. This spectrum was typical of CMC. Gelatin There were gentle peaks typical of a plateau except at wave numbers 497cm-1 (110%T) and 430cm-1 (112%T). Glycerol The initial transmittance was 62%T at 3292cm-1. Several peaks did not resemble the API spectrum. HEC Several peaks observed but the sharpest that was typical of the API was at 122%T (498cm-1). This may indicate compatibility with the API. HPC Several peaks were record but the sharpest was observed at 95%T (1000cm-1). However, the spectrum ends at wave numbers 430cm-1 (77%T). This indicates incompatibility with the API. HPMC Several peaks observed but the sharpest that were typical of the API were recorded at 115%T (473cm-1) and 420cm-1 (134%T). This indicates compatibility with the API. Metoclopramide This was the Active Pharmaceutical Ingredient (API). The sample of Metoclopramide started at 98%T (3500cm-1), the transmittance then dropped at 95%T (3700cm-1), and 90%T (1594cm-1). The sharp peak was then recorded at 106%T of 420cm-1. Na Alginate These excipients attained a maximum transmittance of 146%T at 400cm-1. A wavelength of 456 cm-1 at 115%T was recorded too. This suggests compatibility with the API. NA Saccharine Spectroscopy of NA Saccharine started at 100%T of 1680cm-1 before dropping to 94%T (1643cm-1). These excipients attained a peak of 150%T at 412cm-1 (lowest wavelength). This indicates a compatibility with the drug. Discussion The plots of Transmittance (% T) versus Wave-numbers (cm-1) representing the Infrared (IR) spectrum were obtained. The peaks of transmittance and wave numbers were observed and analyzed for matching and compatibility characteristics. KBr method was used because of its transparency properties in varying wavelengths. Moreover, KBr picks up moisture that shows as broad spectrum eliminates signals from other organic compounds that may be present in the product. This technique is faster and cost effective. Nicolet iSTM 10 FT-IR Spectrometer is a good spectroscopy system with good precision for analysis and verification purposes. When a beam of light is hitting the sample, some of it undergoes a spectacular reflection on the sample surface while another light goes through the sample and resurfaces after continuous reflection and transmission. The films or excipients represented in the charts are the polymeric compositions in which in addition to the polymer, drug, saccharine, flavor and glycerol were added. From the results, films A1 and A3 recorded similar peaks and nearly the same wave numbers as the active ingredient (Metoclopramide). This suggests compatibility between A1 (2% Na Alginate) and A3 (1% Na Alginate + 1% Na CMC). On the other hand, the films A6 (2% Na CMC), A7 (2% Na CMC + 1% HEC), A13 (1% Chitosan: 4% Gelatin (2:1), A14 (1.5% Chitosan: 1% HEC (4:1), A18 (1% HPC + 1% Na Alginate), A19 (1% HPC + 1% Na CMC), A21 (1% HPC + 1% HPMC), and A23 (1% Na CMC + 1% HEC) recorded dissimilar spectra compared with Metoclopramide sprectrum. This indicates that these samples are incompatible with the API. Similarly, Hydroxypropyl cellulose (HPC), Sodium Carboxymethyl Cellulose (CMC), glycerol, and the flavor had differing peaks. Therefore, they were found to be incompatible with Metoclopramide spectrum. Other the samples and excipients that had similar spectra to the API and therefore compatible with Metoclopramide include films A8 (1% Na CMC + 1% HPMC), A10 (1% HPMC), A11 (1% HEC + 1% HPMC), A12 (1% Chitosan: 4% Gelatin (1:1), and A15 (1% Chitosan). In addition, Chitosan, Gelatin, Hydroxyethyl cellulose (HEC), hydroxypropyl methylcellulose (HPMC), Na Alginate and Na Saccharine. Understanding of the nature of interaction and compatibility between drugs and excipients is important in pharmaceutical activities. Some sugars, metals, and organic acids have been associated with excipients impurity properties, which can affect the efficacy and safety of pharmaceutical products (Shah et al, 2012, pp.146). Na Saccharine is used as a sweetener of filler in drug formulations. However, like any other excipient, it can destabilize or stabilize pharmaceutical products. Thus, selection of excipients in the initial stages of manufacturing process would be based on insight on the breakdown mechanisms, desired dosages, and the anticipated delivery system(s). This study aimed to describe actual and potential interactions between Active Pharmaceutical Ingredients (API) like Metoclopramide and excipients like saccharine. Knowledge of such associations is important as a risk reduction measure. Some excipients compatibility experiments use the Binary mix compatibility testing where customized powder mixes are prepared by triturating individual excipients with the active pharmaceutical components after which thermal techniques are used to screen the samples. The powdered sample may be aqueous or non-aqueous (Shah et al, 2012, pp.146). In this experiment, spectroscopic technique was used to prepare and analyze the samples. Unlike binary Mix Compatibility technique, which has high rate of yielding false negative and positive results, spectroscopic methods are more precise and accurate in measurements. Furthermore, they consume more time and resources compared with spectroscopic techniques (Shah et al, 2012, pp.146). The dug and excipients mixes were analyzed using the FTIR and KBr pellet method, which showed extra peaks unlike in the normal interferogram. The spectra generated showed new peaks and there were not missing bands. Therefore, the results indicate compatibility with the chosen excepients. Extra peaks, broadening and narrowing properties were scrutinized. Metoclopramide bands were observed at 400-1600cm-1. The basis of using infrared in the study of excipients causes changes in the dipole of the molecules, which manifest as variation in bandwidths in the spectra. When the functional ingredients and excipients link up, active compounds in the FTIR spectrum demonstrate broadening and shift in the bands indicating presence of a pure drug (Metoclopramide) and compatibility. Conclusion Thorough compatibility properties between the API and excipients must be examined to produce an efficacious and harmless pharmaceutical product that also remains attractive to consumers. This study has examined the drug-excipient compability properties using spectroscopic technic. Metocloropramide was the principal API and samples like HPMC, HEC, HPC, CMC, gelatin, Chitosan, flavor, Na Saccharine, and glycerol were the excepients. From the spectroscopic analysis (FT-IR), it has been established that compatibility only exists between Metoclopramide and Na Saccharine, Na Alginator, HPMC, HEC, Gelatin, and Chitosan. Refrence Shah, J. A., Patel, M.A., Patel, P.A., Patel, K.N. (2012). Formulation and Characterization of Mouth Dissolving Tablet of Metoclopramide. International Journal for Pharmaceutical Research Scholars. 1(2) p. 145-152 Read More