Development of Modified-Release Diclofenac Sodium Capsules Using Blends of Pectin-Clay Multiparticulate Hybrid Systems as Release Retardants

medium, provided the original work is properly cited. A combination of inorganic and organic hybrid systems is of high research interest as they provide novel hybrid systems for the improvement of existing properties, overcoming limitations of the parent materials, and for the optimization of their controlled release potential. Tis study sorted to develop and pharmaceutically assess the release profle of diclofenac sodium using cocoa pod husk (CPH) blended with diferent proportions of either talc or bentonite as multiparticulate composite release modifers. Preformulation investigations of the multiparticulate hybrid systems included pH, swelling index, moisture content, elemental contents, and fow properties. Te FTIR was also used to investigate the compatibilities between pectin and bentonite (PB), pectin and talc (PT), and diclofenac and pectin-talc (DPT), as well as diclofenac and pectin-bentonite (DPB). Te diclofenac content, uniformity of the weight of capsules, in vitro drug release, and the kinetics and mechanism of release of diclofenac from the hybrid systems were also investigated using mathematical models. Te pectin yield was 23.3%, with the water-holding capacities of pectin-talc (PT) and pectin-bentonite (PB) hybrid systems being 6.4% and 5.0%, respectively. Te swelling indices of PTand PB were 110.0 and 130.0 in 0.1M HCL at pH 1.2 and 130.0 and 149.0 in phosphate bufer at pH 6.8, respectively. Tis system was also found to exhibit excellent fow properties, and there were no diclofenac-excipient interactions. All formulated batches passed the pharmacopoeial and nonpharmacopoeial tests. Tey also demonstrated controlled release properties via diferent release kinetics and mechanisms. Tis study shows that the pectin-talc and pectin-bentonite multiparticulate composites could be used as release modifers in pharmaceutical preparations.


Introduction
In pharmaceutical industries, clays such as bentonite and talc are crucial components used as excipients to create composites with other biopolymers for modifed-release drug delivery systems [1][2][3].A combination of inorganic and organic hybrid systems is of high research interest as they provide novel hybrid systems for the improvement of existing properties, overcoming limitations of the parent materials, and for the optimization of their controlled release potential [4].Lately, composites of clays and biopolymers have gained attention as intriguing materials for innovative drug-delivery systems [5,6].Naturally occurring biopolymers such as gums and pectins are usually preferred over their synthetic counterparts in forming composites due to their biodegradability and less toxicity.Pectin hybrid drug-delivery systems are delivery systems which are of most beneft to local pharmaceutical industries either for the development of target release or modifed-release medications.Tus, these systems not only possess the ideal qualities of pharmaceutical excipients but also have versatile use, are readily available locally, and are easily formulated with less sophisticated equipment [3,[5][6][7].
Te therapeutic management of pain and infammation via the use of diclofenac has resulted in several dosage forms for topical, parenteral, and enteral routes.Conventional and controlled-release diclofenac, which are available for oral administration have reported peptic ulceration, renal depression, gastritis, and other side efects [8].Most controlled-release diclofenac preparations use synthetic polymers as drug-release retardants or matrix carriers due to their good fexibility, resistivity, sensitivity, and chemical compatibility [9].However, these synthetic polymers have also been reported to be nonbiodegradable, have poor biocompatibility, and have an expensive processing cost resulting in an overall high cost of the formulation [10].Tese modifed-release dosage forms exist as interventions in an attempt to minimize gastrointestinal toxicity.Hence, there is a need to investigate the use of natural polymers as alternatives in such diclofenac formulations.CPH pectin is rich in polyphenols which have been demonstrated to elicit anti-infammatory, antinociceptive, and antioxidant properties [11].Tese properties could augment the efect of diclofenac when used in this formulation.In addition, pectin has been reported to resist acidic pH and enzymatic actions in the upper gastrointestinal tract [12].However, the hydrophilic nature and the high swelling capacity of the CPH pectin in the gastrointestinal tract may lead to premature release of the drug when solely used as a matrix carrier [12].Nonetheless, a pectin-clay composite would allow for the formation of a new and improved hybrid system with properties which would overcome these setbacks associated with the sole use of pectin as well as modify diclofenac release to suit patient needs [13].Tese hybrid systems may, therefore, enhance the drug's therapeutic efects and reduce the frequency of dosing and side efects, leading to improved patient compliance [14].Furthermore, the gastric protective efect of pectin and clay matrix composites is an added advantage.Tus, pectin, which is a dietary fbre, is useful for strengthening the gastrointestinal mucous layer.Pectin also enhances the immune barrier by stimulating the adhesion of commensal bacteria, which aids in the prevention of infammatory conditions [15].Hence, a combination of pectin and clay may form useful composites that have the potential for modifed-release drug-delivery systems with enhanced bioavailability and drug-release profles [13,16].Tis study sought to investigate the kinetics, mechanism, and in vitro release profle of diclofenac from pectin-bentonite and pectin-talc diclofenac multiparticulate composite capsules formulated via variation of the multiparticulate composite proportions.

Pectin Extraction from the Husk of Cocoa Pod (CPH).
Ripe, as well as mature, Teobroma cacao L. pods were sourced from an experimental plantation of Cocoa Research Institute of Ghana (CRIG) located in Tafo, the Eastern region of Ghana.Te whole pod husk of freshly harvested cocoa pods were separated from the seeds and pulp.Te husks were minced with the aid of a mechanical blender and prepared for the extraction process.Hot aqueous extraction was undertaken at 50 °C as described previously [7].Ethanol was used in precipitating the extract while the fltration process was carried out twice using a double-folded linen clot.A volume of ethanol which is twice the volume of the extract was used to treat the extract.It was then washed thrice to get rid of any impurities which may be present.Te extract was lyophilized (model 7670520, Labconco, USA) under vacuum within 0 mBar-120 mBar at −41 °C after the extraction process was repeated until exhaustion.Te percentage yield was determined after this process.Te lyophilized pectin was packaged with aluminum foil and kept in a ziplock and placed in a desicator.Te packaged pectin was then kept at −4 °C until utilized [7].

Preparation of Granules of Pectin-Clay Multiparticulate
Composite.A quantity of pectin equivalent to 4 g was accurately weighed into a glass beaker.Ten millilitres of hot water was added and stirred.Two grams of bentonite powder was also weighed and added into the pectin solution and the mixture continuously stirred until a colloidal solution was formed.Te formed colloidal solution was dried at 55 °C for 3 h in an oven.Granules were prepared from the dry pectinbentonite (PB) powder mixture .Te prepared granules were stored in a desiccator until needed for further analysis.Tis was repeated for the preparation of pectin-talc (PT) composite granules.

2
Journal of Chemistry Te swelling index, pH, moisture content, compatibility studies, and fow properties of the composite granules were evaluated.

Evaluation of pH, Swelling Capacity, and Moisture
Content of PT and PB Granules.Te pH of a solution of 1% w / v PT and PB was determined in triplicate via the use of a calibrated Eutech pH meter (ECPH70042GS, Netherlands).Te swelling index was assessed by weighing one gram of the respective pectin-clay composite matrix in a twenty-fve millilitre measuring cylinder, and their occupied volumes (V 1 ) were recorded.An amount of 25 mL of distilled water was added to the test samples and were intermittently shaken for 1 h and were then allowed to stand undisturbed for 3 h.Te fnal volume (V 2 ) for each was again recorded [17,18].
Te swelling capacity was determined as shown in the following: To determine the moisture content, 1 g of the respective pectin-clay composite matrix was weighed into three different Petri dishes that had been preweighed after they had been dried at 105 °C in an oven to obtain a constant weight.Te moisture content was determined as the ratio of the weight of loss of moisture to the weight of the multiparticulate composites expressed as a percentage [17,18].

Flow Properties of CPH Pectin-Clay Multiparticulate
Granules.Te bulk and consolidated (tapped) densities (equations ( 2) and (3), respectively) were determined by slowly pouring 3 g of the granules into a 50 mL graduated glass measuring cylinder.Te volume occupied was noted.Tis was subsequently tapped 100 times and the fnal volume was also recorded.Te determined apparent (bulk) and consolidated densities were used to evaluate the Hausner ratio (equation ( 4)) and Carr's index (equation ( 5)).Te fxed-height method was used to determine the angle of repose (equation ( 6)) of the granules for each formulation.Te experiments were carried out in triplicate determinations and their respective mean values were recorded [19].

Bulk density
The angle of repose � tan x − 1 height base radius  .

Elemental Analysis of Granules of the CPH Pectin-Based
Diclofenac Multiparticulate Matrix.Elemental analysis was performed on pellets of hot water solution of the pectin-clay composites which were irradiated with energy-dispersive Xray fuorescence spectrometer (Spectro X-Lab 2000, Kleve, Germany) [20].

Preparation of Granules of the Pectin-Clay Diclofenac
Composite Multiparticulate Matrix.Modifed-release diclofenac pectin-bentonite (DPB) and diclofenac pectin-talc (DPT) hybrid composite capsules containing approximately 50 mg of diclofenac sodium were formulated via the wet granulation technique.Te required respective proportions of CPH pectin (Table 1) for each of the developed formulations for DPB capsules were weighed and dispersed in a sufcient volume of freshly boiled distilled water to form a viscous dispersion of granulating fuid.Te respective quantities of diclofenac sodium, bentonite, and dicalcium phosphate were weighed and mixed via doubling up for each of the DPB formulations (F1-F3), as shown in Table 1.A 2360 µm mesh size sieve was used to screen the various powder mixture.Te required mixed powders for each formulation were mixed in their respective granulating fuids by geometric dilution.After a damped mass was obtained, it was sieved through a 2000 µm•mesh size sieve.Te granules were dried at 40 °C for 1 hour 30 minutes in a hot air oven.After complete drying, the granules for each of the DPB formulations were screened through an 841 µm•mesh and stored in a desiccator.Te abovementioned process was repeated for formulations of DPT multiparticulate composite capsules (A1-A3) using ingredients as shown in Table 1.

Compatibility Studies Using Fourier-Transformed Infrared Spectroscopy (FTIR).
Te PerkinElmer Fourier infrared spectrophotometer (spectrum 2, sr.no.94133, UK) Journal of Chemistry was used to carry out this investigation on bentonite, talc, pectin-clay multiparticulate composites, and pectin-clay diclofenac multiparticulate composites to investigate excipient-excipient and diclofenac-excipient compatibility studies.A maximum force gauge was used to apply the pressure to the test samples on the diamond crystal.A spectrum was generated in the range of 4000 cm −1 -400 cm −1 after scanning the sample twenty-four times [21].
2.9.Formulation of Capsules.Te conventional punch method was used to hand prepare capsules with 300 mg of granules.Te granules were transferred onto the base of the vertically held capsule size "0."Te open end of the capsule was repeatedly pressed until the capsule was full.Te cap was then reinstalled and the capsule was sealed.An empty capsule shell was employed as a counterbalance when adding the granules or withdrawn until the precise weights were measured [7].

Quality Assessment of Modifed-Release Diclofenac Capsules
(1) Uniformity of Weight.An amount of 20 randomly selected capsules from DPB formulation were weighed (SN: AE 436647 Adam Equipment, UK) together and individually as well.Each capsule was completely emptied and the empty shell was weighed and noted.Te net weight of the 20 randomly selected capsules was determined as the diference between the total weight of the 20 capsules and the total weight of the 20 emptied capsule shells.Te net weight of the individual capsules was also obtained via the subtraction of the weight of the individual emptied capsule shell from its respective capsule weight.Tis was repeated for DPT capsule formulation [22].

Development of the Calibration Plot for Diclofenac
Sodium.One gram of diclofenac sodium powder was weighed into a 10 mL volumetric fask, and 5 mL of distilled water was used to dissolve the content in the fask.Te solution was then topped up to volume using distilled water.Solutions of concentrations 400-2100 µg/mL were prepared from the stock solution, and their absorbance was determined using the UV-visible spectrophotometer (Merck, Darmstadt, Germany) at 276 nm.Tis was used to obtain a calibration plot for diclofenac estimation in the subsequent assay and dissolution studies.

Assay of Formulations.
A number of 10 capsules from formulation F1 of DPB multiparticulate matrix were randomly selected and their contents were completely emptied into a porcelain mortar.Te granules were triturated and an amount equivalent to the average net weight of one capsule was weighed into a volumetric fask measuring 50 mL.Te diclofenac sodium was extracted using 50 mL of 50% methanol.Te content of diclofenac in a capsule of F1 from DPB multiparticulate composite capsules was assessed via the use of the UV-vis spectrophotometer (Merck, Darmstadt, Germany) at the wavelength 276 nm.Tis determination was repeated three times and the abovementioned step was repeated for the rest of the formulations of DPB and DPT capsules [23].q.s q.s q.s q.s q.s q.s q.s 4 Journal of Chemistry valorization [20].Solvent systems available in the literature for extraction include hydrochloric acid, nitric acid, and aqueous solvents [20,26].In this study, hot aqueous extraction was chosen because this system is environmentally friendly, safe, biocompatible, and cost-efective and can be easily processed into formulations with less-sophisticated equipment [27].Furthermore, the hot aqueous extract of CPH pectin has shown remarkable applications to suit drugdelivery needs [20].Te yield was 23.3% which is above the reported range of 2%-20% [27,28].Te reported increase in the yield could be as a result of the diference in the extraction conditions.Te pH of 1% w / v solution of both PT and PB composite multiparticulate hybrid systems were 6.1 ± 0.00 and 6.3 ± 0.00, respectively, which are close to neutral pH.Te moisture contents were 6.4 ± 0.5% and 5.0 ± 0.02%, respectively, for DPT and DPB multiparticulate matrices, which was low, suggesting possible protection from microbial degradation and improvement in mechanical properties of the powders [20].Te swelling indices of PT and PB were 110.0 and 130.0, respectively, in 0.1 M HCl at pH 1.2 and 130.0 ± 0.01 and 149.0 ± 1.40, respectively, in phosphate bufer at pH 6.8.Te higher swelling index recorded by DPB multiparticulate composite granules is due to the presence of montmorillonite in the bentonite which has swelling and adsorption properties; for instance, in an aqueous medium, anhydrous montmorillonite becomes a hydrated material and changes to gel with increasing water content.Tis characteristic plays an essential role in modifying the release of drugs from bentonite-based matrix formulations [29].CPH pectin is also reported to swell to varying extents in various media.According to earlier studies, a medium's pH, ionic strength, and salt content all afect how much CPH pectin swells [30].Te swelling behaviour exhibited by the formulated pectin-clay diclofenac sodium is crucial for difusion-controlled drug-delivery systems.

Flow Properties of PB and PT Diclofenac Composite Matrix
Granules.Te results as shown in Table 2 show that the granules have excellent fow properties due to the values obtained for angle of repose, Hausner ratio, and Carr's index.Tis implies that during encapsulation, the granules would fow easily from the hopper to uniformly fll the capsule shell [31].

Elemental Content of the Pectin-Clay Diclofenac
Composite.Elemental analysis of both DPT and DPB composite matrices revealed a rich source of calcium, magnesium, potassium, aluminium, manganese, phosphorus, iron, sodium, zinc, and silicon and other elements such as sulphur, nickel, chromium, and cobalt were present in very minute quantities.Te results obtained (Table 3) are comparable to other reported studies [26][27][28].Te presence of these macro-and microminerals serves as a potential source of nutraceuticals for health benefts such as regulation of metabolic processes when consumed [32].Te mineral contents could also impact on the viscosity and swelling capacity of the matrix as reported [20].

Diclofenac-Excipients Compatibility Studies.
To ascertain the physicochemical integrity of diclofenac sodium in the presence of excipients over the shelf life, compatibility studies were undertaken utilizing FTIR data analysis.Tis is important primarily for the bioavailability of the active pharmaceutical ingredients (APIs) and the safety of the patient.A mixture of materials is said to be compatible if no new functional groups are detected from the FTIR data of the API and excipients before and after formulation [33].
Talc powder showed characteristic sharp peaks at 667 cm −1 and 3675 cm −1 due to O-H bending and O-H stretching, respectively, and a broad strong peak for Si-O stretching at 991.39 cm −1 (Figure 1(a)), which were consistent with the previous report in the literature [34,35].
In the FTIR data for diclofenac sodium (Figure 1(b)), peaks were detected at 3386.67 cm −1 and 1306.89cm −1 for N-H and C-N stretching vibrations, respectively [36].Te broad band observed around 3225.90 cm −1 was characteristic of O-H stretching (of carboxylic acid) and its corresponding O-H bending was the narrow peak at 1383.73 cm −1 .Te carboxylic C�O stretching peak was at 1573.83 cm −1 while those for aromatic C�C stretching vibrations were found at 1505.43 cm −1 and 1551.42 cm −1 as previously reported [36].
In bentonite, the major peaks were observed at 3695.55 cm −1 and 3619.64 cm −1 for O-H stretching due to the silanol group and water, respectively (Figure 1(c)).Te O-H bending peak was detected at 1634.72 cm −1 .Te peaks at 996.31 cm −1 and 514.88 cm −1 were characteristic for Si-O stretching and Si-O bending vibrations, respectively, as suggested in previous reports [37][38][39].
Te spectrum for pectin (Figure 1(d)) revealed a broad band peaking at 3293.90 cm −1 for carboxylic acid O-H stretching vibration, and its corresponding O-H bending vibration at 1435.89 cm −1 is consistence with the reported literature [20].Carboxylic acid C=O was detected at 1605.56 cm −1 .Peaks detected at 1248.01 cm −1 and 1030.87 cm −1 correspond to C-O stretching vibrations for aliphatic ether and alcohols as characteristic of complex polysaccharides [40,41].
Two diferent combinations of diclofenac and pectin with talc or bentonite (labelled P/B/D and P/T/D) were formulated and analyzed by FTIR compatibility studies (Figures 1(e) and 1(f )).Te wave numbers for the relevant peaks of P/B/D and P/T/D have been noted in Table 4. Figure 1(g) shows a comparison of the IR spectrum of diclofenac with those of P/B/D and P/T/D.In both cases of P/B/D and P/T/D, there is a broad band that stretches from In the IR stretching vibration region between 2500 cm −1 and 1500 cm −1 , the absence of any signifcant peaks for P/B/ D and P/T/D relative to the individual components indicates that no new functional groups were formed due to the interaction between diclofenac and excipients.
Furthermore, a comparison of the fngerprint region (1400 cm −1 to 400 cm −1 ) of P/B/D and P/T/D and those of their constituent materials indicated that there were no new functional groups formed.Peaks observed in the fngerprint region can be attributed to the individual materials.For instance, for P/B/D, peaks at 743.90 cm −1 and 1030.14 cm −1 may be due to C-Cl bending vibration in diclofenac and C-O stretching in pectin, respectively, whereas for P/T/D, 666.98 cm −1 and 1009.83cm −1 indicated O-H bending and Si-O stretching vibrations in talc.Altogether, and as clearly illustrated in Figure 1(g), it may be concluded that diclofenac is compatible with the other excipients as no new functional groups were noticed upon FTIR compatibility studies of the formulated granules.

Quality Assessment of Pectin-Clay Diclofenac
Multiparticulate Composites 3.5.1.Calibration Curve for Diclofenac Sodium.Te calibration curve helps to estimate the concentration of diclofenac in the developed formulations.Figure 2 shows that it is linear with the R 2 value of 0.9709, which indicates a good relationship between the absorbance and the concentration of diclofenac sodium.Tis implies that the absorbance values obtained in various determinations could be used to measure the quantity of diclofenac sodium present in the formulations, which is vital for the efcacy of the formulations.

Uniformity of the Weight and Diclofenac Content in
Pectin-Clay Diclofenac Formulations.Te mean capsule weights of the DPB and DPT formulations are as shown in Table 5.All formulations had a percentage deviation of <7.5%, as shown in Table 5. Tis implies that the developed pectin-clay diclofenac capsules met the BP standard for the uniformity of the weight test [42].Tis is as a result of the uniform particle-size distribution of granules and their recorded excellent fow properties which could have led to the even flling of the capsule shell and uniform granule compression after flling, resulting in the passing of this test [21].As a result, it can be seen that the formulations contain even doses of diclofenac sodium between the individual capsules.
Te content analysis of formulations of both DPB and DPTcapsules fell within the acceptable compendia criteria of 85-115%, as shown in Table 5 [22].Terefore, the diferent developed pectin-clay matrix capsules contained the right amounts of diclofenac, which are of allowable pharmaceutical quality.Tis is essential for accuracy in drug administration since the optimal therapeutic outcome is indicative of application of good manufacturing practices (GMPs) in producing quality products.

In Vitro Drug
Release.Diclofenac is a biopharmaceutical classifcation system (BSC) class II drug, characterized by poor water solubility associated with limited and erratic dissolution profles and variable bioavailability.However, the use of cocoa pod husk pectin in the development of pectin multiparticulate composite capsules could elicit a signifcant efect on the release of the medicinal agent with reproducible release profles [43].Analyses of the dissolution profles of the multiparticulate composite    1. C1 exhibited a controlled release profle, suggesting pectin from cocoa pod alone has control-release properties as reported [44].When bentonite was employed in the hybrid matrix, the release profle followed a biphasic pattern with an initial slow diclofenac release followed by a rapid release which could be tailored towards therapeutic needs (Figure 3).Tis property exhibited by the bentonite hybrid system could be associated with montmorillonite, a major component of bentonite, with unique swelling and adsorption properties, that results in entrapment and subsequent drug release [29].Characteristically, the delayed release was inversely proportional to the quantity of bentonite present in the individual formulations (F1-F3).
A similar observation was made when talc was replaced with bentonite in the hybrid matrix; however, it was not characterized by biphasic release (Figure 1).Te characteristic drug release from the talc composite may be indicative of the slow desorption of diclofenac from the interlamellar space and the matrix surface [4].

Kinetic Models and the Mechanism of Diclofenac Release from Multiparticulate Composite Capsules.
Polymeric matrix swelling, material degradation, and diffusion of solutes generally govern the release of drug substance from a polymeric matrix system [25,44].Te rate of polymeric matrix swelling and its subsequent degradation are afected by variations in physicochemical properties; thus, the release kinetics of polymeric systems will be invaluably afected as these phenomena directly afect the API difusion rate.To confrm this, the kinetic and mechanism of diclofenac release were ftted into mathematical models.Information on how the best release kinetics of a drug suits any of the kinetic models are statistically given as R 2 values, as shown in Table 6.Te results show that formulations F2 and F1 follow the zero-order release kinetics with R 2 values of 0.8738 and 0.8417, respectively.Tis implies that the release of diclofenac from these pectin-bentonite diclofenac multiparticulate-composite capsules is independent of the diclofenac concentration in the multiparticulate capsules.As a result, the serum level of diclofenac may remain constant throughout the delivery period.However, the rest of the formulations also followed the Korsemeyer-Peppas release kinetic; thus, the fractional release of diclofenac from the pectin-clay multiparticulate composite is exponentially related to time [44].Among the formulations which demonstrated the Korsemeyer-Peppas kinetic release of diclofenac, formulation C1 was the most optimized formulation due to its recorded highest R 2 value of 0.9989.
Te mechanism of diclofenac release from formulation A1 was via non-Fickian transport (0.45 < n < 0.89), while the rest of the formulations showed a super case II transport mechanism (n > 0.89) for the release of diclofenac from pectin-clay multiparticulate-composite capsules [44].Tis implies that the release of diclofenac from all the developed  Journal of Chemistry formulations except for A1 was via difusion and relaxation of the polymer chain in the pectin-clay multiparticulatecomposite capsules.Tis shows that the diference in the physicochemical properties coupled with the diferent proportions of bentonite and talc afected both the kinetic and release of diclofenac from the multiparticulate composite capsules.

Conclusion
Te ideal physicochemical properties of the pectin-talc and pectin-bentonite composites coupled with their compatibility with other pharmaceutical excipients and the active pharmaceutical ingredient make them suitable candidates to be used in modifed-release formulations.Tis study had the aim of developing and examining oral modifed-release formulations of diclofenac sodium using cocoa pod husk pectin, talc, and bentonite as the natural release modifers.Upon analyzing the results obtained, it can be concluded that all formulations, containing composites of cocoa pod husk pectin or its combination with talc or bentonite, are capable of exhibiting a modifed release of diclofenac sodium.Tus, the formed macroporous structures composed of diferent entities of pectin and bentonite or pectin and talc ofer a novel multifunctional system as a drug-delivery carrier of diclofenac and with desired versatility which could be tailored to meet drug delivery needs, be it sustained release, target release, and controlled release formulations.Tis could result in the potential of making formulations not only capable of reducing dosing frequency, avoiding dose dumping and consequently minimising adverse efects, but also ofers an added advantage of extranutraceutical benefts that also control drug-related adverse efects to ultimately increase patient compliance.

Figure 2 :
Figure 2: Calibration curve for diclofenac sodium at 276 nm in distilled water.
[25]btained data from the in vitro diclofenac sodium release studies were integrated into the mathematical kinetic models (zero order, Higuchi, Korsmeyer-Peppas, frst order, and Hixson-Crowell) to determine the mechanisms of diclofenac sodium release from the pectin-clay matrices.Te model which best describes the kinetics of the release of this drug is the model with the highest correlation coefcient (R 2 )[25].
[24].In Vitro Diclofenac Sodium Release Studies.Te US Pharmacopoeia dissolution type I apparatus (Lid8 Dissolution Tester, Vanguard Pharmaceuticals Machinery Inc., USA) was used to carry out this study in a 900 mL of phosphate bufer, with pH 6.8 per vessel which was set at a temperature of 37 °C ± 0.5 °C with a rotation speed of 100 rpm/min for 5 h.Aliquot of 10 mL of the solution was sampled at 60, 120, 180, 240, and 300 minutes.Tese were replaced immediately with equal volumes of phosphate bufer of pH 6.8.Te sampled solutions were analyzed at 276 nm using UV-vis spectrophotometer (Merck, Darmstadt, Germany) after they have been fltered.Te amounts of diclofenac sodium present were subsequently calculated[24].Triplicate determinations were carried out for each capsule formulation.2.9.5.Drug Release Kinetics.

Table 1 :
Working formula for diclofenac pectin-clay capsules.
3.1.Characterization of the Pectin-Clay Composite Multiparticulate Matrices.CPH pectin is a 1,4 galacturonic acid polymer which is extracted from cocoa pod husk waste via

Table 2 :
Flow properties of the CPH pectin-based diclofenac multiparticulate matrix.
−1to 2500 cm −1 .Tis band is due to the O-H stretching of carboxylic acid.However, the O-H stretching bands in the combinations are more intense than those for pectin, bentonite, talc, or diclofenac individually and this may be due to intermolecular hydrogen bonding.Moreover, the broad nature of the O-H stretching bands in P/B/D and P/T/D overshadowed the individual O-H stretching bands for pectin, bentonite, talc, and diclofenac.

Table 4 :
Characteristic FTIR peaks for the various materials and formulations.

Table 5 :
Uniformity of the weight and diclofenac content of pectin-clay diclofenac multiparticulate matrix capsules.