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Der Pharmacia Lettre, 2011: 3 (5) 173-178
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ISSN 0974-248X
USA CODEN: DPLEB4

Studies on physical /chemical compatibility between synthetic and

herbal drugs with various pharmaceutical excipients
Santanu Mallik,*1 Mahendra D. Kshirsagar,2 Vipin Saini3
1
Mahatma Jyoti Rao Phoole University, Achrol, Rajasthan
2
Dept. of Pharmacy, P. Wadhwani College of Pharmacy Yavatmal, Maharashtra
3
MM College of Pharmacy, MM University, Mullana, Haryana
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ABSTRACT

Stability of Pharmaceutical formulations are oftenly challenged by compatibility between drugs

and excipients. The objective of the present study is to identify compatibility between drug:drug
and drugs:excipient. Curcumin and Tretinoin were selected as model drug where Ethyl cellulose
(EC) and Poly vinyl alcohol (PVA) as excipients. The study was done by Fourier transform
infrared spectroscopy (FTIR), X-ray diffraction study (XRD) and Thin layer chromatography
(TLC). The spectrophotometric graphs revealed that there was no significant changes in position
of functional groups of Curcumin, Tretinoin, EC and PVA (O-H, C=O, C-H str.) in pure drugs
and excipients with respect to their physical mixtures. X-ray diffraction study reflects that the
characteristic peaks of curcumin appeared at a diffraction angle of 2 at 7.950, 8.800, 12.280,
17.290 showing that Curcumin and Tretinoin was present as a crystalline form as well. The Rf
values of the physical mixtures obtained from TLC study on the 0th and 30th day were
approximately similar to the Rf values of the pure Curcumin and Tretinoin. The above
spectrophotometric data and retention factor clearly implies that the synthetic-herbal drug
combinations with pharmaceutical excipients are compatible with each other and can be
introduced for successful development of novel drug delivery system.

Keywords: FTIR, Compatibility study, TLC, Curcumin, Tretinoin, XRD.

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INTRODUCTION

Assessment of drug-drug-excipients compatibility is very important to identify product’s

stability as well as its reproducibility with ensured therapeutic efficacy[1]. Although excipients
selected for pharmaceutical formulations bears no pharmacological significance i.e. inert in
nature[2]. But the excipients may participate in physical and chemical interaction and cause
serious degradation of active pharmaceutical ingredients with poor dissolution rate and non-
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uniformity of dose[3]. Over the decade, various methods have been developed to identify drug-
excipients compatibility. It’s very essential to conduct such studies as a part of formulation
development process[4]. A number of multifactorial diseases like Acne, Psoriasis etc. needs two
or more drug combination for effective treatment[5,6] The definition of combination products
are clearly mentioned by Food and Drug Administration under section 21 CFR 3.2 (e). Multi
drug combination came into light with respect to the patient compliance as well[7,8] The
functional groups within the drug molecule may change the activity of each other, hence alters
the therapeutic affectivity[9].EC is cellulose derivative where some of the hydroxyl groups on
the repeating glucose units are converted into ethyl ether group and is a choice of pharmaceutical
manufacturer due to its good film forming properties[10]. PVA is a excellent film forming and
adhesive properties and prepared by partial or complete hydrolysis of polyvinyl acetate[11].
Various analytical tools viz. FTIR, XRD, SEM, separation technique viz. TLC etc. provides data
indicating alteration in position of functional groups of drug in physical mixtures[12,13,14].

MATERIALS AND METHODS

Fourier transform infrared spectrophotometry study was done with Shimadzu Model (30.000:1),
model no. 3116465 with wave no. range 7800 to 350 cm-1, peak-to-peak, 4 cm-1 resolution, in a
neighborhood of 2,100 cm-1, 1-minute accumulation and having resolution of 0.5, 1, 2, 4, 8, or
16 cm-1. X-Ray diffraction study of drug combination was identified by model XRD-6000,
having the selectivity of independent dual axis θ-2θ linkage drive, independent 2θ axis and θ axis
drives.Tretinoin is obtained from Shalaks Pharmaceuticals Private Limited, New Delhi and
Curcumin is gift sample obtained from RYM Exporters, New Delhi.

FT-IR studies
Sample/KBr ratio
The concentration of the sample in KBr should be in the range of 0.2% to 1%. The pellet is much
thicker than a liquid film, hence a lower concentration in the sample is required (Beer's Law).
Too high a concentration usually causes difficulties obtaining clear pellets. The IR beam is
absorbed completely, or scattered from the sample which results in very noisy spectra[15].

Sample preparation
Completely dried potassium bromide was transferred into a mortar. About 2 % of drug sample
was weighed in digital balance, mixed and grind to a fine powder. Two stainless steel disks were
taken out of the desiccator. A piece of the precut cardboard (in the tin can next to the oven) on
top of one disk was placed and cutout hole was filled with the finely ground mixture. The
second stainless steel disk was kept on top and transfers the sandwich onto the pistil in the
hydraulic press. With a pumping movement, hydraulic pump handle moved downward.
The pistil will start to move upward until it reaches the top of the pump chamber. Then,
the pump handle moved upwards and continued pumping until the pressure reaches
20,000 prf. Rest for a few seconds and with the small lever on the left side, the pressure was
released. Removing of the disks and pulling apart. Obtained film was homogenous and
transparent in appearance. Than inserted into the IR sample holder and attach with scotch tape
and run the spectrum[16].

The physical mixtures of drugs were prepared in 1:1 ratio and then passed through sieve # 30.
Samples of drug and excipients were placed in vial, closed and labelled. Then the vials were
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stored under two different conditions at 4˚C and at 40˚C±75% RH. Observations of all the
mixtures were done on 0th day, 7th day, 15th day and 30th day. The compatibility of drugs with
excipients was studied by FT-IR.

X-Ray Diffractometry
The solid state of the drugs was investigated by X-ray powder difractometry with Bragg-
Brentano geometry at a wavelength of 1.5406. Powder X-ray difractograms were recorded in a
diffraction angle (2θ) range of 20-400 using a step size of 0.030 under an exposure time of
8s[17,18].

Thin Layer Chromatography

The specified amount of drug and cream bases were weighed separately and mixed properly with
the help of spatula. Mixture of drug and cream bases was placed in vial, closed and labelled.
Then the vials were stored under two different conditions at 4˚C and at 40˚C±75% RH.
Observations of all the mixtures were done on 0th day, 7th day, 15th day and 30th day. The
compatibility of drugs with oily bases was studied by thin layer chromatography[19,20].

RESULTS AND DISCUSSION

Data obtained from FT-IR spectrophotometric study clearly indicates insignificant changes in
spectra obtained from physical mixture of drugs and excipients. Spectra obtained from pure
Curcumin were found 1759.41 cm-1 and 3491 cm-1 for C=O and O-H str.(Figure 1) respectively
and in case of Tretinoin it was observed 1685.87 cm-1 and 2937.68 cm-1 (Figure 2) respectively.
FT-IR spectroscopy of drugs shows very close spectra of the pure component 1758.23cm-1 and
1672.24 cm-1 for C=O str.; 3517.78 cm-1and 2933.87 cm-1 for O-H str. (Figure 3) Spectrograph
of both the drugs and excipients physical mixture shows 3517.78 cm-1, 2933.87 cm-1, 3415.69
cm-1 and 3346.43cm-1 for O-H str. group.

Spectrography of C=O str. shows sharp peak at 1758.23 cm-1, 1672.24 cm-1 for Curcumin and
Tretinoin respectively. C-H str. group for EC and PVA indicates sharp peak at 2868.55 cm-1 and
2909.12 cm-1 (Figure 4) respectively. Which indicates no interference between them (Table 2).
There was no major changes in peaks of ketone (C=O), Hydroxyl (O-H) and methyl (C-H), in
reference to the observed value of Curcumin and Tretinoin (Figure 1).

Figure 1: FT-IR interpretation of Curcumin

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Figure 2: FT-IR interpretation of Tretinoin

Figure 3: FT-IR spectra of Curcumin and Tretinoin combination

Table 1: FT-IR spectra of Curcumin and Tretinoin combination

Wave length (cm-1)

S. No. Functional Gr. Standard Curcumin Tretinoin
Absobance Pure drug PM Pure drug PM
1 O-H str. 2700- 3800 3491.72 3507.41 2937.68 2925.22
2 C=O str. 1650-1780 1759.41 1768.11 1685.87 1692.86

Figure 4: FT-IR spectra of Curcumin+ Tretinoin + PVA+EC

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Table 2: FT-IR spectroscopy data of Drugs and excipients
S. F.G. Curcumin+Tretinoin Curcumin+Tretinoin+PVA Curcumin+Tretinoin+PVA+EC
no Standard Curcumin Tretinoin Standard Curcumin Tretinoin PVA Standard Curcumin Tretinoin PVA EC
(cm-1) (cm-1) (cm-1) (cm-1) (cm-1) (cm-1) (cm-1) (cm-1) (cm-1) (cm-1) (cm-1) (cm-1)
1 O-H 2700-3800 3507.41 2925.22 2700- 3800 3529.34 2947.19 3435.43 2700- 3800 3517.78 2933.87 3415.69 3346.43
2 C=O 1650-1780 1768.11 1692.86 1650-1780 1749.56 1703.37 NA 1650-1780 1758.23 1672.24 NA NA
3 C-H 2700-3800 NA NA 2700- 3800 NA NA 2859.87 2700- 3800 NA NA 2868.55 2909.12

F.G.: Functional Group

The powder X-ray diffractograms of pure Curcumin and Tretinoin reveals that characteristic
peaks of curcumin appeared at a diffraction angle of 2 at 7.95, 8.80, 12.28, 17.290 showing
Curcumin was present as a crystalline form. The diffraction patterns of physical mixtures
showed several peaks which is similar to that in pure form, indicating that the crystallinity of
curcumin and tretinoin was not changed (Figure 5).

Figure 5: Powder X-ray diffraction of pure Tretinoin and Curcumin physical mixture

TLC studies showed that the Rf values of the mixture obtained on the 0th and 30th day were
approximately similar to the Rf values of the pure Tretinoin and Curcumin. Therefore, it was
concluded that both the drugs were compatible with each other (Table 3).

Table 3: Compatibility study of Tretinoin and Curcumin by TLC method

Rf values
S. No. Drug 0th day 30th day
4 C 45 C/75% RH 4 C 450C/75% RH
0 0 0

1 Tretinoin 0.959 0.957 0.977 0.974

2 Curcumin 0.776 0.774 0.773 0.778

CONCLUSION

The data obtained from FT-IR spectroscopy, X-Ray diffraction and TLC study clearly indicates
no interaction between drug and excipients, hence synthetic and herbal drug combination is safe
to formulate in a novel dosage form. To identify drug release pattern from novel delivery system,
we will go for cream formulation in future.

REFERENCES

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