Formulation Development and Evaluation of Floating Microspheres of Curcumin

 

Shamal Satish Patil*, Rajendra K. Surawase, Parag D. Kothawade

Department of Pharmaceutics, Loknete Dr. J. D. Pawar College of Pharmacy,

Manur, Nashik 423501, Maharashtra, India.

 

ABSTRACT:

Purpose – There are several approaches that have been developed in order to increase the gastric residence time (GRT) floating drug delivery system is one of them. Floating microspheres improve the bioavailability and releasing for long period of time. In the current investigation curcumin floating microspheres are being developed to extend the drug release. Method - Emulsion solvent evaporation approach is used for development of floating microspheres by using Eudragit RS100, HPMC K100, Ethyl Cellulose as polymers. Acetone and Ethanol was used as a solvent in a ratio of 10:5. Stirring speed of mechanical stirrer was 900rpm. Result - There was no reaction between the drug and excipients according to FTIR analysis. The developed microspheres have virtually spherical shapes and particle size range was between 200 - 420µm. The effectiveness of the drug entrapment was found between 60 - 98.4%. It was found that the buoyancy was between 70 - 92%. The    in-vitro drug release was found to be 99.5 of batch 15. The developed microspheres indicated prolonged drug release of 12hrs. The optimized batch was B15. Conclusion - According to results of the research, developing gastro-retentive floating microspheres of curcumin using the emulsion solvent evaporation method with HPMC K100, Eudragit RS100, and ethyl cellulose is a promising method.

 

 

INTRODUCTION:

A highly effective, durable, and safe-for-consumption target drug concentration in blood or tissue is the main objective of any drug delivery system. The two key components of drug distribution are the direction at which the target is intended and the timing of the delivery.

 

The term "spatial placement" differs from the term "chronological delivery," which refers to managing the rate at which a drug is given to a particular organ or tissue. It may be possible to use a well-designed drug delivery system with a prolonged or controlled release to address these issues.¹ To increase the stomach residence time (GRT) of dosage forms, two techniques have been developed: hydrodynamically balanced systems (HBS) and floating drug delivery systems (FDDS).² Drugs with quick elimination through the blood include those with shorter half-lives and are rapidly absorbed from the gastro intestinal tract (GIT). To prevent such systemic issues, systems for delivering controlled drugs orally were created.³

 

Microspheres that float:

The frequent injection of therapeutic agents used in conventional therapy reduces patient compliance since the medications' interactions not only with the targeted cells but also with healthy, normal cells frequently have unfavourable effects. The therapy requires providing the therapeutic material at high doses in order to maintain its effects. All of these problems with standard treatment can be resolved by controlled drug delivery techniques (Microspheres, Microcapsules, Nanoparticles, Implants, etc.).⁴

 

The floating micro beads are developed from synthetic polymers. Using HPMC, Eudragit, and ethyl cellulose polymers, an emulsion-solvent evaporation method was used to create hollow curcumin microspheres.⁵

 

The ginger family (Zingiberaceae) includes a kind of plant that produces curcumin. It initially originated throughout India but is now spread over the globe, particularly in Southeast Asia, China, and Latin America.⁶

 

It is known to have anti-inflammatory and antioxidant qualities, and it might possibly be useful towards pathogens and bacterial organisms. Additionally, it possesses chemo preventive properties for a number of malignancies, including those of the colon, breast, prostate, esophagus, lung, and oral⁷

 

MATERIALS AND METHODS:

Materials:

Curcumin was obtained from Arti Pharma, L.B.S. Marg, Bhandup (West), Mumbai Eudragit, Span 20, Light liquid paraffin, Acetone, Ethanol was purchased from Balaji Industries. 

 

Methods:

Method of preparation:

The emulsion solvent evaporation technique was used to produce the microspheres. Drug and polymer dissolved in ethanol and acetone. In 100ml of liquid paraffin, 1% span 20 was added and stirred with a propeller. Drop by drop, the drug and polymer solution was introduced to the span 20-containing liquid paraffin. The elimination of the solvent must be completed by stirring for 3 to 4 hours. Microspheres were subsequently separated using watsman filter paper and recovered. To remove the liquid paraffin, the collected microspheres were washed four or five times with 50 ml of petroleum ether and being dried.⁸

 

Table 1: Formulation table of Floating Microsphere of Curcumin

Batch	Drug [mg]	HPMC K100 [mg]	Eudragit RS 100[mg]	Ethyl cellulose [mg]	Liquid paraffin [mg]	Solvent ratio Acetone: Ethanol [ml]
B1	400	50	70	90	100	10:5
B2	400	55	60	90	100	10:5
B3	400	55	60	120	100	10:5
B4	400	55	70	105	100	10:5
B5	400	60	80	105	100	10:5
B6	400	60	70	120	100	10:5
B7	400	55	70	105	100	10:5
B8	400	55	70	105	100	10:5
B9	400	50	60	105	100	10:5
B10	400	55	70	105	100	10:5
B11	400	50	80	105	100	10:5
B12	400	50	70	120	100	10:5
B13	400	55	70	105	100	10:5
B14	400	60	70	90	100	10:5
B15	400	55	80	120	100	10:5
B16	400	60	60	105	100	10:5
B17	400	55	80	90	100	10:5

 

Evaluation parameters:

Calibration curve of Curcumin:

The standard calibration curve for curcumin was created by measuring the absorbance of curcumin in 0.1N HCL at concentrations ranging from 5 to 25µg/ml at 430nm. The resulting curve was then plotted with its absorbance on the y-axis and curcumin level on the x-axis.⁹

 

Compatibility Studies:

With an FT-IR spectrophotometer, drug-excipients compatibility was investigated prior to the development of floating microspheres.¹⁰

 

Micrometric characteristics:

The bulk density at the angle of repose, the tapped density, the compressibility index, and the Hausner's ratio were used to describe the microspheres.¹¹

 

Particle size:

The size of the particles was determined by a microscope equipped with Motic microscope.

 

Percentage yield:

Calculating percent yield. Microspheres that had been completely dried were gathered and precisely weighed. The yield % was then determined.¹²

 

                           Weight of microspheres

% yields = ----------------------------------------  x 100

                              Weight of polymers

 

Efficacy of drug entrapment:

For the purpose of determining how much drug existed, the spheres were crushed in a mortar and pestle to determine their size. 50mg was utilized for the purpose of evaluation. This was extracted using aliquots of hydrochloric acid (HCl) containing 0.1N. Then (pH-1.2) 0.1N HCl solution was added to the 100ml volumetric flask's capacity after the sample was put there. The absorbance was measured spectrophotometrically at a particular wavelength versus a suitable blank after filtration of the solution. The amount of drug entrapped was calculated using the formula below.⁴

 

                                 Practical Drug Content

% Entrapment =  ----------------------------------- X 100

Efficiency               Theoretical Drug Content

 

Evaluation of in vitro buoyancy:

300mg of microspheres were placed on top of a USP XXIV dissolving apparatus type II holding 900ml of 0.1N hydrochloric acid with 0.02% Tween 80. For 12 hours, the medium was agitated with a paddle rotating at 100 rpm. The floating and settling portions of the particles have been acquired, dried out, and analyzed individually. The percentage of microspheres that remained floating in relation to their overall mass was calculated as buoyancy (%).

 

                                 W_F 

Buoyancy (%) ----------------- x 100

                            W_F – W_S

 

 

 

 

In-vitro drug release:

A modified USP XXIV dissolving device type I (basket) was used to evaluate the in vitro dissolution of drugs from the microspheres. The test was performed in independent runs in 900ml of distilled water with 0.1 HCl (pH 1.2) as the dissolving media. Each run was performed at 100rpm. The samples (5ml each) were removed and examined spectrophotometrically at 430 nm at periodic times. The same volume of new medium was added to the release medium in order to keep the sink state constant. Most of the experiments were done in a second instance. The cumulative drug release (%) was calculated utilizing a standard curve.⁸

 

RESULT AND DISCUSSION:

Determination of λ max in 0.1 N HCl and calibration curve:

 

Table 2: Concentration and absorbance forCurcumin in 0.1 N HCl

Sr. No.	Concentration(µg/ml)	Absorbance
1	5	0.187
2	10	0.233
3	15	0.343
4	20	0.429
5	25	0.514

 

Fig 1: Calibration curve of curcumin in 0.1 N HCl

 

Table 3: Micrometric analysis of made-up floating microspheres

Batch	Bulk Density	Tapped Density	% Compressibility	Haunters Ratio	Angle of Repose
B1	0.35±0.12	0.40±0.12	12.5±0.12	1.14±0.12	28.5±0.25
B2	0.37±0.22	0.42±0.12	12.9±1.60	1.14±0.42	28.5±0.22
B3	0.41±0.22	0.45±0.17	8.33±1.18	1.09±0.32	25.5±0.33
B4	0.35±112	0.4±0.16	10.7±0.19	1.12±0.52	26.4±0.22
B5	0.38±0.12	0.41±0.17	7.69±0.10	1.03±1.12	24.3±0.25
B6	0.37±0.32	0.4±0.12	7.40±1.20	1.08±0.12	23.5±0.25
B7	0.35±3.12	0.4±0.15	10.7±0.12	1.12±0.22	26.4±0.22
B8	0.35±0.12	0.4±0.13	10.7±1.35	1.12±1.12	26.4±0.35
B9	0.4±0.22	0.45±0.12	12±0.12	1.13±0.12	27.4±0.28
B10	0.35±1.14	0.4±0.22	10.7±2.18	1.12±0.22	26.4±0.37
B11	0.41±0.18	0.45±0.16	8.3±0.12	1.09±0.12	25.5±0.37
B12	0.4±2.29	0.43±0.22	8.8±1.02	1.08±0.32	25.1±0.25
B13	0.35±0.33	0.4±0.12	10.7±.1.22	1.12±1.12	26.4±0.38
B14	0.37±0.18	0.41±0.12	11.1±0.12	1.12±1.13	27.2±0.27
B15	0.4±0.8	0.43±0.18	8±1.16	1.08±0.13	22.5±0.23
B16	0.38±0.20	0.43±0.16	11.5±1.18	1.13±1.12	26.5±0.35
B17	0.38±0.±0.12	0.43±0.15	11.5±1.15	1.13±2.15	26.5±0.32

 

Table 4: % Buoyancy, Drug Entrapment Efficiency, Percentage Yield, Particle size

Batch No	% Buoyancy	Drug Entrapment	Percentage Yield	Particle size(µm)
B1	74.2±0.12	68.1±0.23	73.7±0.18	389±0.05
B2	70.3±0.22	60.5±1.34	72.7±0.15	313±0.02
B3	85.4±0.34	88.3±2.13	83.4±2.12	325±0.04
B4	83.3±0.55	86.76±0.21	81.74±0.12	345±0.10
B5	89.6±1.12	95.5±0.12	88.3±1.14	420±1.12
B6	91.5±0.24	96.96±.025	90.6±0.16	250±0.14
B7	83.5±1.27	86.76±0.24	81.74±0.14	304±0.08
B8	83.4±0.29	86.76±0.14	81.74±1.12	234±1.05
B9	76.4±0.30	71.01±0.16	74.79±0.14	345±1.5
B10	83.6±3.22	86.76±0.14	81.74±1.12	274±1.06
B11	85.7±0.24	88.3±0.31	83.4±0.12	321±2.24
B12	87.5±0.12	89±0.21	85.9±0.15	300±4.22
B13	83.7±1.22	86.7±0.14	81.74±2.12	270±3.22
B14	78.8±0.33	75.3±0.15	77.4±0.16	290±2.35
B15	92.5±0.12	98.4±0.13	91.60±0.17	200±1.52
B16	80.4±2.35	79.23±0.21	79.2±1.12	370±0.35
B17	80.4±1.26	79.27±0.14	79.2±0.16	364±0.29

 

Table 5: In-vitro Drug Release of formulation (B1 to B6)

Time	B1	B2	B3	B4	B5	B6
1	6.7 ±0.4	5.2 ±1.02	3.7 ±2.01	2.5 ±032	9.1 ±1.19	10.4 ±1.18
2	9.7 ±2.05	11 ±0.25	12.47 ±0.32	12.14 ±1.25	14.32 ±1.22	16.11±0.13
3	18.8 ±2.03	20.3 ±1.98	17.3 ±0.19	24.0 ±1.35	21.16 ±2.84	24.32±1.89
4	24.13 ±2.15	24.41 ±1.35	26.60 ±1.4	29.14 ±2.02	26.11 ±3.32	31.11 ±0.36
5	35.02 ±1.94	38.45 ±0.25	29.21 ±2.32	35.14 ±3.35	36.17 ±1.03	35.21 ±3.93
6	42.12 ±1.04	42.13 ±2.35	35.34 ±3.15	50.65 ±3.16	46.14 ±0.36	40.14 ±2.49
7	47.25 ±1.35	48.51 ±2.08	44.41 ±1.05	56.14 ±2.89	57.47 ±0.15	44.16 ±2.15
8	56.42±0.15	53.41 ±1.54	49.13 ±2.18	63 .11±1.03	62.4 ±3.16	49.11 ±0.52
9	65.14 ±1.06	58.01 ±8.99	52.14 ±1.04	71.14 ±1.73	64.14 ±2.32	61.17 ±2.94
10	67.14 ±2.05	64.48 ±1.02	54.10 ±1.32	79.47 ±1.23	71.41 ±2.16	70.7 ±1.54
11	70.1 ±2.15	68.7 ±2.15	83.5 ±2.03	83.6 ±0.25	82 ±2.87	89.12 ±1.13
12	73.1 ±2.36	69.9 ±2.65	89.14 ±2.04	86.7 ±075	91 ±0.65	92.17 ±2.30

 

Table 6: In-vitro drug release of formulation (B7 to B12)

Time	B7	B8	B9	B10	B11	B12
1	8.4±1.17	15±1.29	5.2±1.02	10.14±2.02	3.7±1.25	16.14±2.15
2	15.12±2.73	23±1.95	8.2±0.13	15.34±1.93	12.14±2.67	21.14±1.68
3	25.32±2.45	29.5±2.46	20.44±1.12	20.32±1.69	17.44±1.47	66.41±2.93
4	29.14±1.15	36.17±2.36	23.32±1.19	25.25±1.88	21.62±1.02	34.74±1.49
5	35.23±1.05	44.19±2.26	36.62±0.13	26.14±0.28	24.41±2.12	43.14±0.35
6	48.14±3.14	53.14±1.60	42.45±2.59	26.62±0.62	35.11±1.67	56±2.95
7	59.71±1.76	59.16±1.36	50.2±3.49	40.12±0.18	41.14±2.94	59.35±1.54
8	68.14±1.34	65.11±0.63	53.12±2.13	56.31±2.19	49.12±1.25	68.14±1.36
9	73.01±2.81	71.17±1.26	56.32±0.59	60.41±2.35	52.22±2.15	73.19±2.18
10	79.14±2.64	83.20±2.07	62.32±2.11	70.12±2.67	68.35±1.14	82.45±2.98
11	88.4±1.39	88.6±2.40	67.2±1.26	77.4±1.33	85.4±1.03	89.7±1.25
12	86.7±2.73	85.2±1.26	69.16±1.39	86.12±0.18	88±1.52	91.14±1.79

 

Table 7: In-vitro drug release of formulation (B13 to B17)

Time	B13	B14	B15	B16	B17
1	3.9±2.28	3±2.18	9.9±1.12	2.4±0.25	2.8±1.19
2	9.7±1.35	8.2±1.28	24.23±1.23	6.7±2.25	24.12±1.94
3	18.14±1.02	24.14±0.15	40.13±1.14	21.13±2.23	26.21±1.45
4	25.17±1.63	26.41±2.95	50.12±0.79	26.45±2.49	32.35±1.18
5	26.35±1.15	38.61±1.68	52.14±2.45	35.45±.2.66	39.44±0.47
6	40.64±1.19	41.47±1.43	65.10±0.74	38.14±1.35	45.36±0.25
7	42.61±1.45	49.62±2.81	68.12±1.74	41.45±1.25	56.41±0.18
8	49.41±1.95	53.14±1.68	82.02±0.36	54.95±1.35	59.31±0.74
9	52.32±2.16	66.71±1.24	85.11±1.03	59.65±2.48	62.47±2.15
10	66.1±2.84	71.32±1.14	89.21±1.69	61.25±1.76	73.69±2.14
11	83.6±1.05	73.14±0.47	90.12±1.14	64.14±1.03	79.11±1.47
12	86.1±2.09	77.17±2.94	99.5±1.18	73.14±2.14	88.17±1.50

 

Fig 2: In Vitro Drug Release Batch B1 to B6

 

Fig 3: In vitro Drug Release Batch B7 to B12

 

Fig 4: In vitro Drug Release Batch B13 to B17

 

CONCLUSION:

In the current research, floating curcumin microspheres were developed. The outcomes of the drug identification tests, which included FTIR, and UV visible spectrophotometric examinations, showed that the substance was pure curcumin. FTIR analysis of the drug and excipients compatibility revealed that there was no interaction. Curcumin’s maximum absorbance was measured at 430nm. Emulsion Solvent Evaporation Approach was employed to produce microspheres Eudragit RS 100, HPMC K100, Ethyl Cellulose these three polymers were used in the formulation. Preparation of floating microspheres required 3 to 4 hours by stirring. The average particle size was in range of 200-420µm smallest particle size was of Batch 5 that is 200 µm and larger particle size was of B15 that is 420µm. Percentage buoyancy of the floating microspheres was in the range 70.3% - 92.5% after 12 hrs and Micromeritic properties Bulk density, tapped density, Carr’s Index, Hausner’s ratio, Angle of repose showed the results in standared range. The study had a drug entrapment efficiency that ranged from 60.5 to 98.4%. According to the results of drug entrapment, formulation B15 had the highest entrapment rate at 98.4%, while formulation B2 had the lowest entrapment rate at 60.5%. The percentage yields for floating microspheres were ranged from 72.7 % to 91.60%. Modified USP XXIV dissolving device type I (basket) was used to evaluate the in - vitro dissolution of drugs within the microspheres. Dissolution was done in 0.1N HCl. The B15 Batch showed maximum drug release that is 99.5% in 12 hours and B9 showed minimum drug release was 69.16%. The results showed that increasing amount of Eudragit RS 100 and HPMC K100 prolong the drug release. It is clear from the study that the emulsion solvent evaporation approach by using HPMC K100, Eudragit RS100, and ethyl cellulose is a promising way to develop gastro-retentive floating microspheres of curcumin.

 

ACKNOWLEDGEMENT:

I am thankful to Prof. R.K Surawase, Prof. P.D Kothawade and Dr. Avish Maru Principal of Loknete Dr.J.D Pawar College of Pharmacy, Manur Tal.Kalwan for their guidance and support

 

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Received on 27.06.2023         Modified on 13.08.2023

Accepted on 11.09.2023   ©AandV Publications All Right Reserved