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ORIGINAL ARTICLE
Year : 2019  |  Volume : 11  |  Issue : 3  |  Page : 321-328  

Design and development of microparticulate delivery system for Curcumin


Department of Pharmacognosy, Dr. D. Y. Patil Institute of Pharmaceutical Science and Research, Pune, Maharashtra, India

Date of Web Publication22-Aug-2019

Correspondence Address:
Prof. Aditi Shrinivas Kulkarni
Department of Pharmacognosy, Dr. D. Y. Patil Institute of Pharmaceutical Science and Research, Pimpri, Pune - 411 018, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pr.pr_24_19

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   Abstract 


Background: Curcumin has been associated with remarkable beneficial effects; despite having a broad spectrum of activities, curcumin is characterized by poor water solubility and low bioavailability. Objective: The objective of this study is to enhance the solubility of curcumin using polyethylene glycol 400 (PEG400) and establish a microparticulate drug delivery system in a sodium alginate polymer matrix (microspheres containing curcumin triturated with PEG400 [Cur-PEGMS]) to improve the bioavailability of curcumin. Materials and Methods: The microspheres were formulated using the ionic gelation technique. Nine batches (F1 to F9) were prepared using 32 factorial design. The amount of sodium alginate and calcium chloride was selected as a formulation variable. The prepared Cur-PEGMS were characterized by Fourier-transform infrared spectroscopy, scanning electron microscope, differential scanning calorimeter, ultraviolet spectrophotometer, and high-performance thin-layer chromatography (HPTLC). The pharmacokinetics of curcumin was characterized in rats using high-performance liquid chromatography, and calculations were performed using WinNonlin standard edition version 1.1 software. Results: We found that solubility was affected by the use of cosolvent. All F1–F9 batches were investigated for entrapment efficiency, and batch F5 was found to be optimum batch which was further evaluated. HPTLC chromatogram of Cur-PEGMS shows peak retention for curcumin. The particle size of microspheres was found to be in the range of 384–468 μm. Remarkable improvement in maximum plasma concentration and bioavailability was observed. Maximum the time after administration of a drug when maximum plasma concentration is reached (Tmax) was found to be 0.5 h, and AUC0–24was found to be 374.75 ng/ml and 622 ng/ml for curcumin suspension and curcumin microspheres, respectively. Conclusion: The developed formulation enhances the bioavailability of the drug. This enhanced oral absorption of Cur-PEGMS may provide a practical formulation to conduct a correlative pharmacodynamic study.

Keywords: Curcumin, factorial design, microspheres, pharmacokinetics, sodium alginate, polyethylene glycol 400


How to cite this article:
Kulkarni AS, Bhujbal SS. Design and development of microparticulate delivery system for Curcumin. Phcog Res 2019;11:321-8

How to cite this URL:
Kulkarni AS, Bhujbal SS. Design and development of microparticulate delivery system for Curcumin. Phcog Res [serial online] 2019 [cited 2019 Nov 20];11:321-8. Available from: http://www.phcogres.com/text.asp?2019/11/3/321/265049



SUMMARY

  • Curcuma longa (turmeric) is widely used Indian spice that imparts color and flavor to food. Curcumin is a polyphenol and principal curcuminoid present in turmeric. Curcumin has been reported to have wide range of pharmacological activities such as antioxidant, anti-inflammatory, antimicrobial, anticancer, antioxidant, antidiabetic, antihyperlipidemic, and hepatoprotective activities. Despite number of pharmacological activities, curcumin exhibits low aqueous solubility. The earlier pharmacokinetic studies indicated poor bioavailability and instability of curcumin. To overcome these problems, a number of novel delivery systems have been tried. Based on the solubility studies, in this study, curcumin solubility was enhanced with polyethylene glycol 400 and then it was encapsulated in sodium alginate matrix. The concentration of polymer and the concentration of cross-linker were selected as formulation variables to prepare nine batches of formulation using 32 factorial design. The batch F5 was found to be optimum batch and was further characterized by scanning electron microscopy, high-performance thin-layer chromatography, Fourier-transform infrared spectroscopy, and particle size analysis. The pharmacokinetic parameters were determined in rats using WinNonlin standard edition version 1.1 software. An increase in AUC0– and maximum plasma concentration of curcumin in microspheres compared to curcumin in suspension was observed after oral administration. The solubilization method and the enhanced absorption of curcumin in formulation may provide a solution to overcome the limitation of curcumin and offer an opportunity for efficient use of it.




Abbreviations Used: PEG: Polyethylene glycol, PEG200: Polyethylene glycol 200, PEG400: Polyethylene glycol 400, PEG600: Polyethylene glycol 600, FTIR: Fourier-transform infrared spectroscopy, SEM: Scanning electron microscopy, UV: Ultraviolet spectrophotometer, Cur-PEGMS: Microspheres containing curcumin triturated with PEG400, HPLC: High-performance liquid chromatography, HPTLC: High-performance thin-layer chromatography, DSC: Differential scanning calorimetry, %DEE: Percentage of drug entrapment efficiency, SMEDDS: Self-microemulsifying drug delivery system, PLGA: Poly (lactic-co-glycolic acid), Std.: Standard, AUC: Area under curve, Cmax: Maximum plasma concentration, Tmax: Maximum the time after administration of a drug when maximum plasma concentration is reached, Plasma Conc.: Plasma concentration, %EE: Percentage of entrapment efficiency, SD: Standard deviation,

IS: Internal standard, Rfvalue: Retention factor value, ng: Nanogram, μg: Microgram, μm: Micrometer, mg: Milligram, ml: Milliliter, mm: Millimeter, cm: Centimeter, m: Meter, g: Gram, Kg: Kilogram, i. d.: Internal diameter.


   Introduction Top


Curcumin is a yellow-colored, hydrophobic polyphenolic pigment derived from the rhizomes of spice–herb turmeric or Curcuma longa L., belonging to the family, Zingiberaceae.[1] Curcumin (1,7-bis-[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione: Diferuloyl methane) is insoluble in water and ether but is soluble in ethanol, dimethyl sulfoxide, and other organic solvents. C. longa L. contains curcuminoids; the three major components of curcuminoids are curcumin (77%), demethoxycurcumin (17%), and bisdemethoxycurcumin (3%).[1],[2],[3] Turmeric is a food additive, especially in India and Indian subcontinent. It is used as a coloring and flavoring agent.[3],[4] Traditionally, turmeric has been used for the treatment of skin wounds, inflammations, and tumor.[4] Curcumin has been reported to exhibit various activities [5] such as antioxidant,[6] anti-inflammatory,[7],[8] antimicrobial,[9],[10] anticancer,[11],[12] antioxidant,[13] antidiabetic, antihyperlipidemic, and hepatoprotective activities.[14],[15],[16],[17]

However, previous studies indicated that low water solubility, rapid metabolic elimination, resulting in poor bioavailability after oral administration.[18] Various formulation techniques have been designed to improve the oral bioavailability of curcumin. For example, curcumin-loaded liposomes with an average size of 100–150 nm were prepared that showed improved activity compared to free curcumin.[19] In another study,[20] curcumin liposomes result in a reduction in tumor growth. The self-microemulsifying drug delivery system for curcumin exhibits increased dissolution and improved bioavailability.[21] Various different polymeric nanoparticles were prepared with the aim to increase the efficiency of curcumin and have versatile pharmacokinetics, and it includes curcumin encapsulated poly (lactic-co-glycolic acid) (PLGA)[22] and polyethylene glycol (PEG).[23],[24] Curcumin-loaded PLGA nan-particles [25] were studied for the kinetics of tissue distribution and blood–brain barrier penetration. Colon-targeted microspheres of curcumin [26] showed prolonged drug release. Another gastroretentive floating drug delivery system was designed for curcumin [27] and tested for chronic and acute inflammation. Carrier-mediated drug delivery system where chitosan and alginate blended with cloisite 30B [28] was reported for controlled release of curcumin. A micronized form of curcumin exhibits significantly improved bioavailability.[29] Calcium alginate beads for colon-specific delivery containing self-emulsifying curcumin were developed, and cytotoxic activity was evaluated against human colon adenocarcinoma cell lines (HT-29).[30] Curcumin-PEG complex followed by encapsulation with chitosan–gelatin nanoparticles [31] was designed that exhibits improved bioavailability. Recently, curcumin was encapsulated to improve the stability and solubility in water using supercritical antisolvent technology.[32]

The entrapment of poorly water-soluble drug in the microparticulate drug delivery system has been extensively studied using various polymers and techniques.[33] Sodium alginate is a natural occurring hetero-polysaccharide from marine brown algae. It is a hydrophilic, high molecular weight, nontoxic, and biodegradable polymer composed of 1,4-linked-β-D-mannuronic acid and α-L-guluronic acid residues. Sodium alginate gels in the presence of divalent cation like calcium, and this technique is known as ionotropic gelation technique or cross-linking mechanism.[34],[35]

Based on the investigations, in the present study, solubility of curcumin in PEGs was first optimized and then curcumin-PEG complex was encapsulated in alginate beads (microspheres containing curcumin triturated with PEG400 [Cur-PEGMS]). The process and formulation variables were optimized so as to obtain the highest curcumin encapsulation. The statistical design was used in this study to analyze the influence of these variables on properties of formulation. In this work, the studied variables were concentration of polymer and concentration of cross-linker. Further, the physicochemical parameters including morphology, particle size, percentage of drug entrapment, and cumulative drug release were described. The pharmacokinetic parameters of Cur-PEGMS were also investigated in rats, and samples were analyzed by high-performance liquid chromatography (HPLC).


   Materials and Methods Top


Authentic samples of curcumin purchased from Changsha Staherb Natural Ingredients Co., Ltd., China, and internal standard (IS) emodin was obtained from Natural Remedies Pvt. Ltd. Bengaluru, India, used as such without further purification. Acetonitrile (HPLC grade) and acetic acid (Analytical grade) were purchased from Merck Specialties Pvt. Ltd. (Mumbai, India), and HPLC grade water obtained from ELGA LabWater (Model: PURELAB UHQ-II) was used in the analysis. Other chemicals such as sodium alginate, calcium chloride, and PEG400 were purchased from LOBA Chemie Pvt. Ltd. Mumbai, India.

Determination of solubility of curcumin in water

To determine the amount of curcumin solubilized in water, curcumin (100 mg) was triturated with the increasing proportion of PEG200, PEG400, and PEG600 (0.2, 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 ml). The physical mixture (0.5 g) was dissolved in 10 ml of water and filtered, and the absorbance of the resulting solution was read [Figure 1] at 424.5 nm on ultraviolet (UV)–visible spectrophotometer (Shimadzu UV-1800 instrument). The optimum proportion of the drug to the polymer was established from the proportion yielding the maximum amount of solubilized curcumin in water.
Figure 1: Ultraviolet spectrum of standard curcumin (10 μg/ml)

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Preparation of curcumin–polyethylene glycol–alginate microspheres

The Cur-PEGMS were prepared by ionic cross-linking technique. Ionic gelation involves cross-linking in the presence of multivalent counterions. The stock solution was prepared by dispersing 0.5 g of curcumin and previously triturated with 2 ml of PEG400 into appropriate volumes of sodium alginate (2% w/v) in deionized water. The Cur-PEGMS were prepared by dropwise addition of sodium alginate dispersion via 20-gauge hypodermic needle fitted with a 10 ml syringe into 100 ml of 3% w/v of cross-linking agent, calcium chloride solution, with a distance of 5 cm. The process continued for 10 min with a stirring rate of 200 rpm (Remi Motors, Mumbai, India). The droplets from the dispersion instantaneously gelled. The formed microspheres were further allowed to stir in the solution of cross-linking agent for 15 min. The beads were washed with 3 × 50 ml volume of deionized water and were thereafter air-dried until a constant weight was obtained.

Drug-excipient compatibility study

Visual inspection: Drug and polymer were mixed, and color of their physical mixture was observed.

Fourier-transform infrared spectroscopy studies

The Fourier-transform infrared spectroscopy (FTIR) spectra of curcumin, sodium alginate, and prepared Cur-PEGMS were taken by 4 cm −1 resolution FTIR spectrophotometer (Shimadzu R prestige 21) [Figure 2] over the spectral range of 450–4000 cm −1. Each sample was first mixed with fused potassium bromide in a ratio 1:100, and the prepared pallet was placed to determine FTIR spectra.
Figure 2: Fourier-transform infrared spectroscopy spectra of curcumin, sodium alginate, and curcumin formulation (microspheres containing curcumin triturated with polyethylene glycol 400)

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Differential scanning calorimetry of curcumin formulation

The formulation was analyzed by differential scanning calorimeter (Mettler-Toledo star 822e system, Switzerland). The thermograms of curcumin and Cur-PEGMS were obtained [Figure 3] over a temperature range 50°C–200°C at a scanning rate of 10°C/min.
Figure 3: Differential scanning calorimetry of curcumin (standard) and prepared microspheres containing curcumin triturated with polyethylene glycol 400

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Statistical design

To evaluate the effects of variables and interrelationship among them, a 32 factorial design was studied. The factorial design helps to attain maximum information and reduce the number of trials. The amount of polymer, sodium alginate (1–3 g), and cross-linking agent, calcium chloride (1–5 g), was defined as independent variable that varied at low level (−1), medium level (0), and high level (1). The percentage of drug entrapment efficiency (%DEE) was selected as a dependent variable (response). The response surface regression analysis generates a mathematical equation using Design-Expert® (version 10.0.6; StatEase Inc., USA) software [Figure 4].
Figure 4: Contour plot showing combined effect of sodium alginate and calcium chloride on percentage of entrapment

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Percentage of drug entrapment efficiency

The loaded Cur-PEGMS (100 mg) were ground in a mortar and dispersed in methanol. The mixture was placed in a sonicator for about 3 h. Then, the solution was filtered through a 0.45-μm membrane filter. The dilutions were prepared, and drug content was then determined [Figure 5] using UV–visible spectrophotometer (Shimadzu UV-1800) at 424.5 nm. The regression equation derived from standard graph was then used to calculate %DEE with the following formula:{Figure 5}

Drug entrapment efficiency = (Actual drug content/Theoretical drug content) × 100

Imaging through high-resolution digital scanning microscope

The images of Cur-PEGMS were taken using a digital microimaging adaptor with SAGLO soft software (SAGLO Research Equipments, India). Randomly chosen microparticles were observed [Figure 6] for their individual shape and morphology. Microparticles were visualized under ×25 magnification.
Figure 6: High-resolution digital imaging of microparticle at ×25

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Particle size analysis

Particle size measurement of prepared formulation, Cur-PEGMS, was carried out with an optical microscope. Stage micrometer was used to calculate the calibration factor. The particle size was calculated by measuring randomly chosen 100 particles with the help of calibrated ocular micrometer.

Scanning electron microscopy

The surface morphology of the Cur-PEGMS was examined by scanning electron microscopy (SEM) [Figure 7]. The dry microspheres were placed on carbon stub coated with gold in an ion sputter and scanned using Carl Zeiss Supra 5 model (Germany). The voltage provided was between 5 and 10 kV. SEM shows almost spherical particles with rough and nonporous surface.
Figure 7: (a)Scanning electro micrograph of prepared microspheres (b) surface morphology of prepared microspheres

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Curcumin estimation in formulation by high-performance thin-layer chromatography

The samples were spotted in the form of bands of a width of 6 mm with space between bands of 8.2 mm, with a 100 μL sample syringe (Hamilton Bonaduz, Switzerland) on precoated silica gel aluminum plate 60 F254 (10 cm × 10 cm) with 250-μm thickness (E. Merck, Darmstadt, Germany) using a CAMAG Linomat 5 sample applicator (Switzerland). The slit dimensions of 5 mm × 0.45 mm and the scanning speed of 20 mm/s were employed. The linear ascending development was carried out in 10 cm × 10 cm twin trough glass chamber (CAMAG, Muttenz, Switzerland) using ethyl acetate: methanol (8.5:1.5 v/v) as mobile phase. TLC plates were dried in a current of air with the help of a hair drier. After the development of plate, densitometric scanning was performed [Figure 8]a and [Figure 8]b on CAMAG thin-layer chromatography scanner at 425 nm for all developments operated by winCATS software version 1.4.2 (CAMAG, Switzerland).
Figure 8: (a)2D densitogram of Track 3 (standard curcumin, 400 ng/band). (b) 2D densitogram of Track 9 (curcumin in sample, microspheres containing curcumin triturated with polyethylene glycol 400)

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Pharmacokinetic analysis

A pharmacokinetic study was performed in male albino Wistar rats (approximately 200 g). According to the standard ethical conditions, all the rats were provided with ad libitum. A free access to standard laboratory diet and water was provided throughout the experiment. The ethical clearance was obtained from the Institutional Animal Ethical Committee, and the procedures were performed according to a protocol. Two groups of rats (each group had at least six rats) were administered curcumin (5 mg/kg) and curcumin formulation suspended in 2% gum acacia (equivalent to 5 mg/kg of curcumin). Blood samples (0.5 ml) were collected in ethylenediaminetetraacetic acid-coated bottles through retro-orbital route during a dosing interval at the following times: 0 (prior to drug administration), 0.5, 1, 2, 4, 6, 10, 12, and 24 h postdose. Samples were centrifuged for 30 min at 1300 rpm to collect plasma and then frozen at −20°C until analysis. The stored plasma samples were analyzed for curcumin concentrations by HPLC. with UV (Jasco HPLC system consisting of Jasco PU-2080 Plus HPLC pump and PU 2075 Plus detector and Jasco Borwin PDA 1.2 version software) detection under the above-mentioned conditions. All values were expressed as mean ± standard deviation (SD).

High-performance liquid chromatography

The standard stock solution of curcumin and emodin was prepared (1000 μg/ml). The stock solution of curcumin was further diluted with acetonitrile to get series of working standard solutions having concentration 10, 20, 50, 100, 200, 300, 400, and 500 ng/ml. Emodin stock solution was further diluted to 10 ml with acetonitrile to get standard solution of concentration 2 μg/ml. A volume of 0.25 ml of each working standard solution of curcumin (0.2–2 μg/ml) was transferred into a series of Eppendorf tubes (Eppendorf-Netheler-Hinz, Hamburg, Germany) containing 0.25 ml of rat plasma, separately. In each flask, 0.25-ml stock solution of emodin (2 μg/ml) was added and 0.25 ml of acetonitrile was added prior to HPLC analysis [Figure 9]a and [Figure 9]b. Such pretreatment is required to remove protein and potential interferences. Tubes were vortexed for 10 min on vortex mixer and then centrifuged for 30 min at 3500 rpm. The peak area ratios of curcumin to emodin were calculated, and the calibration curve was plotted of response factor against concentration of drug.
Figure 5: Percentage entrapment efficiency of different formulation batches (F1–F9)

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   Results and Discussion Top


Curcumin is a polyphenolic compound with number of pharmacological activities, but it exhibits poor bioavailability. One of the crucial factors is its poor solubility that limits the utilization of curcumin. The improvement in oral bioavailability of curcumin was found to be associated with improved aqueous solubility.[18],[36] The past few years witnessed a continuous progress in the research of incorporation of curcumin in novel delivery systems such as liposomes, microemulsifying delivery systems, nanoparticles, solid dispersion, polymeric formulations, nanodisks, and nanotubes.[33],[37] However, in the present work, an attempt was made to use PEG as a cosolvent system for improvement in the solubility of curcumin and subsequent incorporation of curcumin into alginate matrix. PEG is a nontoxic, biocompatible cosolvent. Here, PEGs with different molecular weights have been used. A homogeneous solution of curcumin-PEG was obtained with PEG200, PEG400, and PEG600. As shown in [Table 1], the curcumin concentration in solution was found to be improved with increasing percentage of PEG. The PEG400 and PEG600 have shown comparable solubilization potential. However, PEG600 cosolvent system after entrapment in the alginate matrix shows leaching, so, for further studies, PEG400 cosolvent system was optimized and subjected for preparation and evaluation of formulations.
Table 1: Effect of increasing the concentration of polyethylene glycol 400 on solubility of curcumin in water

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Fourier-transform infrared spectroscopy

The chemical structure of curcumin contains the functional group OH which is indicated by its peak at 3496.16 cm −1 [Figure 2]. It also contains the functional group C = O at 1615.75 cm −1. Peak at 1497.34 cm −1 indicates the presence of aromatic C = C group. Other characteristic peaks of curcumin include 1033.88 cm −1 and 1280.78 cm −1. In the sodium alginate spectrum, 1735.99 cm −1 corresponds to stretching vibrations of C = O and The band around 1028 cm −1 corresponds to C-O-C stretching vibrations. The peak 1458.23 cm −1 was indicating asymmetric starching vibrations. After loaded with curcumin, the formulation resembles similar peak pattern of sodium alginate; however, characteristic peaks of curcumin were found to be masked. Overlying spectra of curcumin, polymer, and its formulation indicate no physical interaction and thus were found to be compatible. This indicates entrapment of curcumin in polymer matrix.

Differential scanning calorimetry

The differential scanning calorimetry (DSC) studies were demonstrated on pure curcumin and encapsulated curcumin beads [Figure 3]. The DSC study indicates sharp endothermic peak for pure curcumin at 175.64°C, while such sharp peak was not observed for the formulation. This may be due to the encapsulation of curcumin into polymeric matrix.

Statistical analysis

The preliminary batches were prepared to obtain distinct microsphere. The concentration of polymer and the concentration of cross-linking agent were selected as independent variables. The formulations were evaluated for percentage of drug entrapment. On the basis of this preliminary study, further 9 formulation batches (F1–F9) were prepared by applying 32 factorial design. It was found that increasing concentration of sodium alginate resulted in increased viscosity and that affects encapsulation process. The increased entrapment efficiency was observed in the formulations (F3, F5, and F6) with an increase in the polymer concentration [Table 2]. However, manufacturing of microspheres became difficult as the concentration of alginate increases to 3%. This may be due to the increase in the viscosity of alginate solution. At low calcium chloride concentration (1% w/v), the formulation showed deformed particles whereas, at a concentration of 3% w/v (F5), the particles gelled rapidly with 84.24% entrapment efficiency [Figure 5]. A higher concentration of calcium chloride (5% w/v) solution as a cross-linking agent adversely affects entrapment efficiency [Figure 4]. This may indicate that above a certain level of increase in concentration of cross-linking agent does not improve entrapment efficiency.[35],[38]
Table 2: Statistical design

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Particle size and surface morphology by scanning electron microscopy

The particle size distribution was found in microrange 384–468 μm. The shape and surface morphology was studied by SEM. The SEM micrographs [Figure 7] indicate almost spherical surface beads with the rough surface area.[39]

High-performance thin-layer chromatography

Various compositions of mobile phase were tried; the mobile phase, ethyl acetate: methanol (8.5:1.5 v/v), gave a dense and compact spot. The identification of curcumin in Cur-PEGMS was carried out by matching the Rf values of curcuminoids in formulation with standard tracks. The Rf value for standard curcumin was 0.87, whereas the Rf value for curcumin in Cur-PEGMS was 0.85. No chemical interaction with the polymer or due to entrapment was confirmed from retention of the peak in the chromatogram [Figure 8]a and [Figure 9]b.

Pharmacokinetic analysis

Plasma samples were analyzed for curcumin concentrations by HPLC with UV detection under the above-mentioned conditions. All values were expressed as mean ± SD. To determine the pharmacokinetic parameters, the plasma concentration and time profiles were compared.

The chromatograms [Figure 9]a showed that retention times for curcumin (in microspheres) and emodin (as IS) were 9.291 and 5.672 min, respectively, whereas retention times for curcumin in suspension and for IS were 9.255 and 5.778 min, respectively [Figure 9]b. No obvious interference peaks were located at the retention times of analyses in the blank chromatograms. Thus, HiQ Sil C18 (250 mm × 4.6 mm internal diameter, 5 m) column with the mobile phase of acetonitrile: 5% acetic acid (70:30 v/v) provided optimum separation for curcumin with these analytical parameters. There is an improvement in maximum plasma concentration in curcumin microspheres compared to curcumin suspension. Maximum the time after administration of a drug when maximum plasma concentration is reached (Tmax) was found to be 0.5 h [Figure 10]. AUC0–24 was found to be 374.75 ng/ml [Table 3] and 622 ng/ml [Table 4] in curcumin suspension and curcumin microspheres, respectively, indicating marked improvement in bioavailability of the formulation of 165.87%.
Figure 10: Pharmacokinetic profile (concentration vs. time) of curcumin and curcumin microspheres

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Table 3: Area under the concentration calculations for curcumin suspension

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Table 4: Area under the concentration calculations for curcumin in microspheres containing curcumin triturated with polyethylene glycol 400

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It can be concluded that better bioavailability of formulated curcumin may be attributed to better solubility and low first-pass metabolism. Similar conclusions were noted in the literature.[21],[22],[23],[40]


   Conclusion Top


In this study, curcumin microspheres were prepared using ionic gelation technique. Our studies showed that the formulation offers better bioavailability and such formulation provide practical solution to overcome limitations and can be extrapolated for further studies.

Acknowledgment

The authors are thankful to Dr. Shridharkumar Biradar, BLDEA's SSM College of Pharmacy, Bijapur, Karnataka, India, for their providing technical assistance and motivation during the work.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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