Inclusion Complexation of Curcumin with Beta Cyclodextrin to Imp
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Der Pharmacia Lettre

Research - Der Pharmacia Lettre ( 2021) Volume 13, Issue 9

Inclusion Complexation of Curcumin with Beta Cyclodextrin to Improve Solubility

Simachal Panda* and Sreemoy Kanti Das
Department of Pharmacy, Lincoln University College, DarulEhsan, Malaysia
*Corresponding Author:
Simachal Panda, Department of Pharmacy, Lincoln University College, DarulEhsan, Malaysia, Tel: +919668222244, Email: [email protected]


Curcumin is an antidiabetic, anti-bacterial, anti-inflammatory, antioxidant drug having low solubility due to its crystalline nature. Drug is coming under class II BCS classification. Here it is an attempt to improve solubility by inclusion complexation method. For this research work cyclodextrin was used. Cyclodextrin is derived from starch. It of different types alpha, beta and gamma cyclodextrin. Depending upon number of sugar moiety cyclodextrins is classified. β Cyclodextrin used in research work for complexation with Curcumin . X ray Diffraction study was conducted for both pure drug and complex. The pure drug shows sharp peaks in graph which reflects nature of crystallinity. Inclusion complexation was done by Physical mixture and kneading method. Volume, temperature and solvent were optimized. After complexation micromeritics and in vitro dissolution tests were conducted, this gave satisfactory results. Calibration curve was done with distilled water. Phase solubility study was conducted.


FTIR, Phase solubility, BCS, Crystallinity, Amorphous.


Curcumin is a drug used for multiple purpose. It also helps to prevent nerve problem, blindness, kidney damage. It keeps blood sugar low. More than 400 million people across the world under the threat of diabetes [1-4]. It’s having anti-inflammatory effect. The solubility of drug is least in aqueous medium and under BCS class II. Effects of curcumin for diabetic patients are needful and helpful. So combined therapy for diabetes is effective. The study is designed to improve the aqueous solubility by different techniques. Both drugs having challenges for formulations. Solid dispersion can improve the solubility of curcumin [5]. The curcumin can be enhanced its solubility by complexation. It can be formulated by enhancing its dissolution rate. As there as not still studied the combined formulation of complexed formulation with the said techniques, it is important to study the comparative study of drug with complexation and non-complexed active ingredients the successful study may lead to cost effective formulations with an effective formulation for mankind [6].

Materials and Methods


The list of apparatus and instruments used in this research are listed below (Table 1).

Table 1. Apparatus and instruments.

SL. No. Apparatus Source
1 Analytical balance Adair Dutta, AD-50 B, Kolkata
2 Glass wares, beakers, separatory funnel Borosil
3 Magnetic stirrer Remi magnetic stirrer
4 Syring Dispovan
5 Sonicator Probe Sonicator
6 UV/VIS. Spectroscopy Systronic double beam 2203 smart spectrophotometer
7 Powdered – XRD Phillip analytical X-ray BV (PW3710) X-ray Diffractometer
8 Dissolution Apparatus USP 8 basket Digital Test Apparatus Lab India (Disso-2000) Mumbai
9 Sieve set ASTM Standard Sieves, SISSO, India
10 Distillation apparatus Borosil
11 Shaker water bath Remi shaker water bath
12 Incubator Thermoline laboratory incubator

Micromeritics study-density measurement

Bulk density: First 1 gm drug is weighed accurately and kept in a clean dry graduated measuring cylinder. Then after pouring the dug in to the cylinder, the granular bed made uniform without disturbing much [7]. The volume map measured directly from the granulation. Measured volume is called as bulk volume. The density is called as bulk density.


Tapped density: After measuring bulk volume of the same measuring cylinder is subjected to tap really 200 times by hand. Then volume was detected. This volume is called as tapped volume.


Flow properties

Angle of repose: A glass funnel having tip cut horizontal to the surface was fixed at constant height around 2 cm with the help of a stand and on the tip one graph paper was placed 2 gm of the drug was weighed and directly poured at a time through the funnel [8]. So the granules formed a conical structure having a height. The weight of the firmed core way measured with the help of scale and the perimeter of the core was marked with the help of marker [9]. From this average radius of the formed circle was measured by drawing various diameter through the center, the angle of repose was calculated by the following formula [10].



ɵ=Angle of repose.

h=height of the formed cone.

r=radius of the circular base on the formed cone (Table 2).

Table 2. Flow properties with angle of repose.

Angle of repose in degree Flow property
<25 Excellent
25-30 Good
30-40 Passable
>40 Very poor

Carr’s index: It is one of the most important parameter to characterize the nature of powder and granules (Table 3).

Table 3. Carr’s index and flow property relationship.

Carr’s index Types of flow
5-15 Excellent flow
12-16 Good flow
18-21 Fair to passable flow
23-35 Poor flow
33-38 Very poor flow
>40 Extremely poor flow


Hausner’s ratio: It is an important character to determine the flow property of powder and granules.


Value less than 1.25 indicates good flow and greater than 1.25 indicates poor flow.

Results and Discussion

Illuriation on micromeritics study of pure drug

Micromeritics of the study of the pure drugs and their results were reported in the (Table 4).

Table 4. Accurate experimental results of the micromeritics study-density measurement.

Experiment Result
Bulk density 0.1742 gm/ml
Tapped density 0.2632 gm/ml
Carr’s index 33.82%
Hausner’s ratio 1.51
Angle of repose 33.52°

Sieve analysis: An accurate weighed 2 gm quantity of drug was subjected to granulometric study using sieves 22, 30, 44, 60, 80, 100 and 120 using a sieve shaker. Drug is sieved nearly around 10 minutes than the sieves are removed from the sieve shaker and powder retained in each sieves was calculated in percentage form using initial weight taken. The results were given below (Tables 5-7, Figures 1 and 2).

Table 5. Sieving analysis.

Sieve no. Retained amount of drug (in mg) Percentage retained (%)
22 0.926 46.3
30 0.33 16.5
44 0.176 8.8
60 0.168 8.4
80 0.016 0.8
100 0.101 5.05
120 0.01 0.5
Total 1.727 86.35

Table 6. Calibration curve of drug with pH 7.4 buffer solution.

Concentration (mcg/ml) Absorbance
0 0
5 0.076
10 0.191
15 0.298
20 0.396
25 0.492
30 0.611
35 0.728
40 0.836
45 0.939
50 1.043

Table 7. Dissolution data of pure drug in distilled water.

Sl.NO. Time %DR
1 0 0
2 2 0.76
3 4 1.9
4 6 2.75
5 8 5.63
6 10 8.25
7 20 15.6
8 30 20.18

Figure 1. Dissolution of pure drug in distilled water.Dissolution of pure drug in distilled water.Image


Figure 2. Phase solubility studies of drug and β -CD.

Methodology optimization

Physical mixture method: Drug and beta-cyclodextrin in the ratio 1:2 was taken and were mixed thoroughly with constant trituration, passed through sieve no. 100 and stored in a desicator.

Kneading method: Drug and beta-cyclodextrin in the ratio 1:2 was taken and to it 20 ml methanol was added and were mixed till a thick slurry was obtained with constant trituration, then it was dried at 45°C, passed through sieve no.100 and stored in a desicator (Tables 8-11, Figures 3 and 4).

Table 8. Drug content in pH 7.4 buffer.

Method % Drug content
Physical mixture method 83.82
Kneading method 85.62

Table 9. Estimation of drug content of drug complex in pH 7.4 buffer.

Sample Volume of methanol Percentage
A 25 55.12
B 20 85.62
C 15 85.05

Table 10. Physicochemical characterization of complex.

Parameters Complex Pure drug
Bulk density 0.294 gm/ml 0.1742 gm/ml
Tapped density 0.384 gm/ml 0.2632 gm/ml
Compressibility index 23.43% 33.82%
Angle of repose 30.068 33.52
Hausner’s ratio 1.306 1.51

Table 11. Comparative dissolution data of kneading mixture, physical mixture, pure drug with distilled water.

Time(min) %DR(PM) %DR(KM) Pure Drug(PD)
0 0 0 0
2 8.3 11.58 0.76
4 17 30.29 1.9
6 24.1 35.89 2.75
8 37.5 40.09 5.63
10 44.21 47.2 8.25
20 61.48 75.74 15.6
30 65.94 86.43 20.18

Figure 3. Comparitive dissolution data of kneading mixture, physical mixture, pure drug with distilled water.


Figure 4. FTIR study.


According to World Health Organization (WHO) reports from 1980 to 2016 the people of diabetes rose from 108 million to 422 million. Between 2000 to 2016 death rates below the age of 18 increased to 5%. Diabetes plays an important role in failure of kidney, blindness, Heart attack. According to WHO diabetes is the seventh leading cause of death. The potent drug curcumin may plays an important role if it will more soluble. The result is satisfactory and it can be formulated in new dosage form along with anti-diabetic drug.