Int J App Pharm, Vol 14, Issue 3, 2022, 49-55Original Article

PREPARATION AND EVALUATION OF GELLAN GUM-LINSEED GUM BLEND MICROBEADS FOR SUSTAINED RELEASE OF ACECLOFENAC

SITANGSU MAITY1*, SANTOSH KUMAR MAHAPATRA2

1Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, Mayurbhanj 757086, Odisha, India, 2Department of Pharmaceutics, Institute of Pharmacy and Technology, Salipur, Cuttack 754202, Odisha
Email: sitangsu02@gmail.com

Received: 20 Nov 2021, Revised and Accepted: 14 Mar 2022

ABSTRACT

Objective: The objective of the current investigation was to design aceclofenac encapsulated microbeads using gellan gum and linseed gum blends following ionotropic gelation by trivalent Al3+-ions as cross-linking agent.

Methods: Various formulation parameters like polymer-polymer blend (gellan gum and linseed gum), proportion and concentration of aluminium chloride (i.e., cross-linker) were considered for preparation of different formulations. In vitro aceclofenac release from these microbeads was performed in 0.1 N HCl (pH 1.2) for a preliminary 2 h, and after this period, it was continued in phosphate buffer (pH 7.4) for the next 6 h (a total of 8 h).

Results: These gellan gum-linseed gum microbeads of aceclofenac exhibited drug encapsulation efficiency of 27.70 ± 0.42 to 74.27±2.57 % and average sizes of gellan gum-linseed gum microbeads were ranged 739.57 ± 22.70 to 968.07 ± 42.24 µm. The release of drug (in vitro) from these gellan gum-linseed gum microbeads of aceclofenac demonstrated a sustained pattern of drug-releasing (over 8 h).

Conclusion: These gellan gum-linseed gum microbeads can be used as an effectual option of polymeric carrier matrices for sustained release.

Keywords: Linseed gum, Gellan gum, Aceclofenac, Microbeads, Sustained release

© 2022 The Authors.Published by Innovare Academic Sciences Pvt Ltd. This is an open-access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/)
DOI: https://dx.doi.org/10.22159/ijap.2022v14i3.43652. Journal homepage: https://innovareacademics.in/journals/index.php/ijap

INTRODUCTION

During past few decades, extensive researches have been done on the successful exploitations of natural gums in drug delivery as natural gums are readily accessible from natural origins, sustainable production, biodegradability and biocompatibility [1-3]. Natural gums are extracted from (i) plant, (ii) marine and (iii) microbial resources [4-24]. Since long, natural gums are being used as excipients for various dosage forms [27-29]. Gellan gum is extracted as a fermentation product of Psedomonus eloda and used as a biopolymer due to its hydrophilicity, gelation capability, biocompatibility, biodegradability, etc [30-32]. It is used in nanoparticles, microparticles, beads, hydrogels, films, etc [26, 33]. The gellan gum structure entails the tetrasaccharide of glucose, glucuronic acid and rhamnose (2:1:1) [34]. Deacetylated gellan gum experiences ionotropic gelation by Ca2+, Al3+, etc., which is used to develop polymeric beads [34, 35]. The ionotropically gelled gellan gum beads have been reported to exhibit rapid drug-releasing due to low mechanical strength in the intestinal pH (alkaline) [35, 36]. To counter such a problem, the blending of other biopolymers with deacetylated gellan gum to prepare ionotropically gelled beads has been researched [34, 35]. The present work was an attempt to design and evaluate the ionotropically gelled microbeads of deacetylated gellan gum and linseed gum blends for sustained drug releasing.

Linseed gum is extracted from linseeds (Linum usitatisimum; family: Linaceae) [37, 38]. On acid-catalyzed hydrolysis, linseed gum yields D-xylose, L-arabinose, L-galactose, L-rhamnose, D-galacturonic acid and D-glucose [22]. It is reported as neutraceutical and antidiabetic [39, 40]. It has also been investigated as tabletting excipients, matrix former, gel former and mucoadhesive [22, 38-42]. Considering the sustained drug releasing property of it, in the present research, the efficacy of linseed gum as release retardant blends with anionic natured deacetylated gellan gum to design ionotropically gelled gellan gum-linseed gum microbeads for sustained release was studied. Previously, any research work on gellan gum-linseed gum microbeads has not been performed till date. Hence, the designing of Al3+ion-induced gellan gum-linseed gum microbeads can be an option for sustained delivery of drugs over a prolonged period. Aceclofenac was investigated as model drug. Its plasma elimination half-life is about 4 h and the recommended dose of aceclofenac is given as 200 mg/daily in divided dosing [11, 43]. Therefore, the current research was aimed to design and evaluate Al3+ion-induced ionotropically gelled gellan gum-linseed gum microbeads for controlled releasing of aceclofenac.

MATERIALS AND METHODS

Materials

Aceclofenac (Drakt Pharmaceutical Pvt. Ltd., India), aluminum chloride (Merck Ltd., India), deacetylated gellan gum (SRL India Ltd., India) and acetone (Merck Ltd., India) were employed. Linseed gum was extracted from linseeds (Linnum usitatisimum), which were purchased from Jharpokharia local market (Dist: Mayurbhanj, Odisha, India) in November 2019. All other chemicals and reagents used in the current research were of analytical grade and commercially available.

Extraction of linseed gum

In the present work, linseed gum was extracted using the method which was previously reported by Hasnain et al. (2018) [22]. Demineralised water (1 L) and linseeds (250 g) were soaked for overnight at room temperature and, afterward, warmed using a water bath until the formation of slurry. After cooling of the formed slurry, it was placed inside a laboratory refrigerator for overnight for the settlement of materials present as undissolved. The supernatant portion of the solution was carefully decanted and then concentrated using a water bath at 45±2 °C to 1/3rd of the initial volume. At room temperature, the concentrated solution was cooled and then taken in a beaker containing thrice the volume of acetone. The formed precipitated material was washed employing acetone. After that, it was repeatedly washed using demineralized water. The finally washed gum precipitated material was dried in a tray dryer for 12 h at a temperature of 45±2 °C. The extracted dried gum was crushed and grinded to a fine powder. Fine gum powder was also passed across an 80 mesh screen and finally, the obtained linseed gum was stored in air-tight desiccators for further study.

Preparation of Al3+-ion induced ionotropically gelled gellan gum-linseed gum microbeads of aceclofenac

Briefly, aqueous solutions of extracted linseed gum (at a temperature of 45±2 °C) and aqueous gellan gum solutions (at a temperature of 60±2 °C) were prepared using a tabletop magnetic stirrer at 400 rpm for 30 min. Both the gum solutions were mixed together with stirring at 500 rpm for 30 min to prepare gellan gum-linseed gum solution mixtures. The polymer concentration of 2 % w/v was maintained in all the solution mixtures. Then, aceclofenac (required amount maintaining the aceclofenac to polymer ratio-1: 2) was added into prepared gellan gum-linseed gum solution mixtures and all the gellan gum-linseed gum mixtures containing aceclofenac were separately homogenized using a homogenizer (Remi Motors, India) at 600 rpm for 30 min. The gellan gum-linseed gum-aceclofenac dispersions were extruded drop-wise in the aluminum chloride (ionotropic crosslinker) aqueous solutions through 18-G extruder needle and the extruded droplets were retained for 10 min to produce wet al.3+-ion induced gellan gum-linseed gum microbeads of aceclofenac. The wet beads were collected by decanting the solution and thoroughly washed for 2 times by demineralised water. After that, washed microbeads were dried using tray dryer at 45±2 °C for overnight. The dried Al3+-ion induced ionotropically gelled gellan gum-linseed gum microbeads of aceclofenac were stored in air-tight desiccators for further study. Formulation.

Determination of drug encapsulation efficiency (DEE)

Microbeads of aceclofenac were sampled and powdered employing clean pestle-mortar. For each formulation, microbeads powders (10 mg) were taken and placed in a volumetric flask containing 500 ml phosphate buffer (pH 7.4). After overnight stay at 37±2 °C, the solution mixtures were stirred, separately, using table top magnetic stirrer at 500 rpm for 30 min. The solutions were filtered by means of Whatman® filter paper (No. 40). The aceclofenac contents in the solution were estimated using a Double-beam UV-VIS spectrophotometer (Shimadzu, Japan) at 274.5 nm wavelength against the appropriate blank solution. DEE (%) of gellan gum-linseed gum microbeads containing aceclofenac was estimated by the formula [19]:

DEE (%) =

Particle size measurement

Average particle sizing of 100 dried gellan gum-linseed gum microbeads of aceclofenac was measured by an optical microscope (Olympus) with a micrometer, which was previously calibrated using a stage micrometer [19].

Scanning electron microscopy (SEM) analyses

The samples of gellan gum-linseed gum microbeads of aceclofenac were coated by gold sputter and SEM photographs were taken using a scanning electron microscope (JEOL Ltd., Japan) operated at the acceleration voltage of 20 kV.

Fourier transform-infrared (FTIR) spectroscopy

Using a set of clean pestle and mortar, various samples were powdered, separately and these were analyzed using a FTIR spectroscope (Shimadzu, Japan) as the pellets made of potassium bromide and samples (99: 1). These pellets were separately placed one by one in the sample holder and the spectral scanning was operated within the wavelength range 4000-400 cm-1and 1 cm/sec scan speed.

Differential scanning calorimetry (DSC)

The moisture free samples (approximately 7 mg) were taken and placed inthe pan made of platinum crucible-aluminium in hermetically sealed condition and ∞-alumina powders as reference substance was employed. DSC thermograms for each tested samples were taken and analyzed in a differential scanning calorimeter (Perkin Elmer®, Japan)atthe heating rate of 10 °C/min under the constant flow of nitrogen gas(flow rate of 150 ml/min).

In vitro aceclofenac release study

In vitro aceclofenac releasing from various gellan gum-linseed gum microbeads of aceclofenac was performed employing the basket type dissolution rate test apparatus (Campbell Electronics, India). The basket of the dissolution apparatus was covered by the nylon cloth of 100 mesh. The temperature of the dissolution system was 37±0.5 °C under and the speed of basket shaft was 50 rpm. Gellan gum-linseed gum microbeads of aceclofenac equivalent to aceclofenac of 100 mg were placed with the basket and immerged in 900 ml 0.1 N HCl (pH 1.2). In vitro aceclofenac release from these microbeads was performed in 0.1 N HCl (pH 1.2) for a preliminary 2 h, and after this period, it was continued in phosphate buffer (pH 7.4) for the next 6 h (a total of 8 h). At the regular time, aliquots (5 ml) were sampled from the dissolution vessel and instantly, the same volume of fresh dissolution medium was replaced to maintain the sink condition. The sampled aliquots were filtered and for aceclofenac contents estimated by a UV-VIS spectrophotometer (Shimadzu, Japan) at 274.5 nm wavelength against the appropriate blank solution.

Analyses of in vitro aceclofenac release kinetics and release mechanism

The data of aceclofenac releasing (in vitro) from gellan gum-linseed gum microbeads of aceclofenac were analyzed by important kinetic mathematical modelling and their squared correlation coefficient (R2) was compared to analyze the accuracy [44-45].

Zero-order equation: M =

First-order equation: M =

Higuchi equation: M =

Korsmeyer-Peppas equation: M =

Where M is the cumulative content of aceclofenac released in time t,

M0 is the start value of M,

k0, k1, kh and Kk-p are the aceclofenac releasing rate constants for zero-order, first-order, Higuchi and Koresmeyer-Peppas equations, respectively. The aceclofenac release exponent (as an indicative of drug-releasing mechanism) was designated as ‘n’. For the spherical matrices, n ≤ 0.43is the indicative of Fickian mechanism (as indicative of diffusion control mechanism). The n value within the range 0.43-0.85 is designated as the non-Fickian mechanism (as indicative of anomalous transport-based release mechanism); whereas n ≥ 0.85 is the indicative of case-II transport mechanism (as indicative of relaxation controlled mechanism) [46, 47].

Statistical analysis

All other data were estimated and analyzed by performing simple statistical analyses using MedCalc software, version 11.6.1.0 (trial version).

RESULTS AND DISCUSSION

DEE

The DEE (%) of Al3+-ion-induced gellan gum-linseed gum microbeads containing aceclofenac was found in-between the range, 27.70 ± 0.42 to 74.27±2.57% (table 1). From the result, it has been noticed that DEE (%) of these gellan gum-linseed gum microbeads (encapsulated with aceclofenac) was significantly controlled by the investigated formulation parameters: crosslinker (here aluminium chloride) concentration in the crosslinking solutions, polymer-blend (gellan gum-linseed gum) contents and ratio (p<0.05). The encapsulations of aceclofenac in the gellan gum-linseed gum microbeads was found to be enhanced with the increments of polymer contents used (i.e., gellan gum and linseed gum) in the polymer-blends and decreasing crosslinker concentration in the crosslinking solutions. The augmentation of DEE in these gellan gum-linseed gum microbeads could be due to viscosity increment of gellan gum-linseed gum blend solutions by increasing polymer contents, which might have been obstruct the aceclofenac leaching from microbeads to the crosslinking solutions [30, 31]. The decreasing encapsulation of aceclofenac with the increment of crosslinker concentration in the crosslinking solutions can be authorized by the reality that the aqueous content might be expelled out from the gellan gum-linseed gum based ionotropically gelled matrices as the ionotropic gelation proceeds [19]. The higher degrees of cross-linking might also cause the convective loss of aceclofenac amounts in these ionotropically gelled biopolymeric microbeads during preparation.

Table 1: Formulation parameters of different Al3+-ion induced ionotropically gelled gellan gum-linseed gum microbeads of aceclofenac with DEE (%) and sizes of microbeads (average diameter, μm)

Code Formulation parameters Average diameter (μm)c
Polymers

AlCl3 (%)

in crosslinking solution

 DEE (%)a,b
Gellan gum (mg) Linseed gum (mg)
B-1 280 50 5 36.75 ± 1.12 911.47 ± 32.12
B-2 280 50 3 51.29 ± 1.44 927.42 ± 34.87
B-3 280 0 5 29.25 ± 0.57 780.16 ± 23.47
B-4 280 0 3 37.01 ± 1.05 826.34 ± 30.22
B-5 250 50 5 30.60 ± 0.48 832.57 ± 28.48
B-6 250 50 3 45.74 ± 1.36 881.08 ± 30.17
B-7 250 0 5 27.70 ± 0.42 739.57 ± 22.70
B-8 250 0 3 39.54 ± 0.98 812.50 ± 27.84
B-O 280 100 2 74.27±2.57 968.07 ± 42.24

aDEE (%) = drug encapsulation efficiency (%), b(Mean ± SD; n = 3), cMean± SD; n = 100.

Particle size

The average particle sizing of formulated gellan gum-linseed gum microbeads of aceclofenac was in-between739.57 ± 22.70 to 968.07 ± 42.24 µm (table 1). Bigger sizing was noticed when polymers (gellan gum and linseed gum) were increasingly used and crosslinker concentration was decreased in the crosslinking solutions. This result could be attributed by the conception of hydrodynamic viscosity [34, 35]. During preparation, when polymers (gellan gum and linseed gum) were increasingly used, larger droplets of gellan gum-linseed gum blend solutions could pass via the needle mouth to the crosslinking solutions. The higher degrees of crosslinking by higher concentrations of crosslinker (aluminium chloride) in the crosslinking solutions produced the smaller-sized microbeads, which could be explained by the fact of contraction of gelled gellan gum-linseed gum matrices by the higher concentrations of crosslinker via availing more concentrated Al3+ions. The obtained results of the current study are in agreement with some of the published reports [19, 30, 31, 34, 35].

SEM analyses

SEM photograph of ionotropically gelled gellan gum-linseed gum microbeads of aceclofenac (B-O) is shown in fig. 1. SEM photograph indicating surface morphology of gellan gum-linseed gum microbeads at the 200 x magnification demonstrated irregular shaped non-agglomerated microbeads having a rough and corrugated surface. In addition, some traces of polymeric debrises were also observed on the microbead surface, which might be caused by means of instantaneous preparation of formation of ionotropically gelled gellan gum-linseed gum microbead matrices.

Fig. 1: SEM photograph of ionotropically gelled gellan gum-linseed gum microbeads of aceclofenac (B-O)

FTIR spectroscopy analyses

FTIR spectra of gellan gum, linseed gum, gellan gum-linseed gum microbeads without aceclofenac, gellan gum-linseed gum microbeads of aceclofenac (B-O) and aceclofenac (pure) are shown in fig. 2. The FTIR spectrum of gellan gum presented different characteristic peak at3630.8 cm-1(due to stretching of–OH groups), band at 2920–3300 cm-1(due to C-H stretch), peak at 1663.5 cm-1(due to C=O stretch), peak at 1403.6 cm-1(due to methyl–C-H bond)and peak at 889.7 cm-1(due to-C-O stretch of alkyl ether group) (fig. 2a). The FTIR spectrum of DG showed the characteristic peaks at 3622.8 cm-1because of–OH stretch, peak at 1735.2 cm-1for cyclic ketones and peaks at 1514.1 cm-1for aromatic–NO2 (fig. 2b). The FTIR spectrum of gellan gum-linseed gum microbeads without aceclofenac presented majority of the characteristic peaks and bands of both the polymers (linseed gum and gellan gum) present in the polymer-blends employed lacking any significant changes (fig. 2c). The FTIR spectra of pure ACE showed characteristic peaks and bands, such as band at 3317.6 cm-1(because of secondary N-H rocking vibrations), peaks at 3029.6 cm-1(because of aromatic-C-H stretch vibration) and at 2939.8 cm-1(due to aliphatic-C-H stretch vibrations), a sharp band at 1770.7 cm-1(due to C=O stretching of carboxylate), a band at 1717 cm-1(due to C=O stretching vibration) and a sharp peak at 717.5 cm-1(due to stretching vibration of 1, 2 di-substituted C-Cl) (fig. 2d). The FTIR spectra of the ionotropically-gelled gellan gum-linseed gum microbeads of ACE (B-O), various characteristic bands and peaks, which were already appeared in the individual spectra of linseed gum, gellan gum and pure aceclofenac without any significant changes and shifting (fig. 2e). From the obtained results of the FTIR spectroscopy analyses this result clearly demonstrates that no chemical/physical interaction was occurred in-between the polymer-blend (gellan gum and linseed gum) used and aceclofenac. Therefore, it is evident that Al3+-ion induced ionotropically gelled gellan gum-linseed gum microbeads of aceclofenac (B-O) had maintained the significant properties of pure aceclofenac, even after the encapsulation within the gellan gum-linseed gum microbeads.

DSC analysis

DSC thermograms of aceclofenac (pure) and gellan gum-linseed gum microbeads of aceclofenac (B-O) are shown in fig. 3. These DSC thermograms indicated the physical states of pure aceclofenac and aceclofenac encapsulated within ionotropically-gelled gellan gum-linseed gum microbeads of aceclofenac (B-O). The DSC thermogram of aceclofenac (pure) demonstrated a comparative sharp typical endothermic peak at 153.53 °C (fig. 3, a), indicating the transition melting point temperature of aceclofenac. In contrast, the DSC thermogram of gellan gum-linseed gum microbeads of aceclofenac (B-O) (fig. 3, b) demonstrated a weaker endothermic peak at 143.57 °C, which indicated that the comparatively amorphous dispersion of aceclofenac within the gellan gum-linseed gum microbeads in comparison to that of pure aceclofenac. The shifting of sharp endothermic peak (noticed in the DSC thermogram of pure aceclofenac) to the broader endothermic peak at the low temperature. This fact can be attributed to the transfer of comparatively amorphous state of aceclofenac after the encapsulation of aceclofenac by gellan gum-linseed gum microbeads formulated via ionotropic gelation induced by Al3+-ions.

Fig. 2: FTIR spectra of: (a) gellan gum, (b) linseed gum, (c) gellan gum-linseed gum microbeads without aceclofenac, (d) gellan gum-linseed gum microbeads of aceclofenac (B-O) and (e) aceclofenac (pure)

Fig. 3: DSC thermograms of (a) aceclofenac (pure) and (b) gellan gum-linseed gum microbeads of aceclofenac (B-O)

In vitro aceclofenac release

Different Al3+-ion-induced gellan gum-linseed gum microbeads of aceclofenac (B-1 to B-8, and B-O) demonstrated in vitro sustained aceclofenac releasing over a prolonged period (8 h) (fig. 4). The in vitro release of aceclofenac from gellan gum-linseed gum microbeads was found to be relatively slower in 0.1 N HCl (pH 1.2) and next, a speedy releasing of aceclofenac was estimated in phosphate buffer (pH 7.4). This fact could be because of rapid swelling of ionotropically gelled gellan gum-based microbeads in higher (alkaline) pH in comparison with that of the lower (acidic) pH and this occurrence might led to a relatively rise in the aceclofenac release, in vitro, in the alkaline pH. The trivalent Al3+ions, which were participated in the inotropic gelation of gellan gum-based microbeads, could not only be displaced by monovalent Na+ions but also be sequestered by phosphate (PO42-) ions contained in phosphate buffer (pH 7.4). This fact might produce the loose and soluble gelled structure of gellan gum-based microbeads when these might be exposed to in the alkaline medium (pH 7.4) [19]. At the preliminary phase of the study, the utmost content of aceclofenac released from gellan gum-linseed gum microbeads of aceclofenac could probably be because of the crystals of aceclofenac, which were adhered onto the microbead surface. Retardation of aceclofenac releasing, in vitro, by this ionotropically gelled gellan gum-linseed gum microbeads was noticed with increasing contents of gellan gum and linseed gum as this might increase the hydrophilic characteristics of the gellan gum-linseed gum blends in these microbeads, which might generate the viscous natured polymeric gels on the surface of these gellan gum-linseed gum microbeads to produce blockade the surface pores onto the microbeads of aceclofenac to facilitate the aceclofenac releasing in a sustained pattern over a prolonged time. Furthermore, the retardation of in vitro aceclofenac releasing from the gellan gum-linseed gum microbeads of aceclofenac formulated with higher aluminium chloride concentration could be attributable to the fact that free volume of ionotropically gelled gellan gum-linseed gum matrices might be decreased and the hindering movements of solute through the gellan gum-linseed gum matrices at the higher degree of ionotropic crosslinking, when increased content of crosslinker was used [19].

Fig. 4: In vitro release of aceclofenac from gellan gum-linseed gum microbeads (B-1 to B-8 and B-O) (mean±SD; n = 3)

In vitro aceclofenac releasing results of gellan gum-linseed gum microbeads of aceclofenac (B-1 to B-8, and B-O) were tested for curve-fitting by kinetic mathematical modelling (table 2). When the respective R2values were compared, zero-order model was found to be best-fit for the microbeads B-2 (R2 = 0.9875), B-3 (R2 = 0.9893), B-4 (R2 = 0.9861), B-5 (R2 = 0.9975), B-6 (R2 = 0.9846), B-8 (R2 = 0.9929) and B-O (R2 = 0.9911). Furthermore, Korsmeyer-Peppas model was found to be closer as the best-fitto zero-order model for the microbeads B-2 (R2 = 0.9605), B-3 (R2 = 0.9773), B-4 (R2 = 0.9502), B-8 (R2 = 0.9654) and B-O (R2 = 0.9627). On the other hand, the first-order model was followed by gellan gum-linseed gum microbeads B-1 (R2 = 0.9869) and B-7 (R2 = 0.9879) as best-fitting. However, zero-order model was found to be closer as the best-fit to the Korsmeyer-Peppas model for the microbeads B-1 (R2 = 0.9727), and B-7 (R2 = 0.9740). The values of release exponent (n) estimated from the aceclofenac releasing results (in vitro) of gellan gum-linseed gum microbeads of aceclofenac (B-1 to B-8, and B-O) and these ranged from 0.8075 to 0.9727. Gellan gum-linseed gum microbeads B-2, B-3, B-5, B-6, and B-O presented the ‘n’ values range in-between0.8825 to 0.9727 indicating that the aceclofenac releasing was occurred by the super case-II transport mechanism; whereas, ‘n’ values for microbeads B-1 and B-4 were near about 0.85 (0.8470 and 0.8461, respectively). This result might be attributed to the dissolution, enlargement and/or relaxation of the ionotropically gelled gellan gum-linseed gum matrices. On the other hand, gellan gum-linseed gum microbeads B-7 and B-8 microbeads exhibited ‘n’ values range less than 0.85 (0.8115 and 0.8075, respectively) indicating the non-Fickian releasing mechanism (anomalous transport). This result might be attributed to the diffusion and swelling controlled releasing of the aceclofenac from these gellan gum-linseed gum microbeads [19, 31].

Table 2: Results of curve fitting of the in vitro aceclofenac release data from Al3+-ion-induced ionotropically gelled gellan gum-linseed gum microbeads of aceclofenac

Models Formulation code
B-1 B-2 B-3 B-4 B-5 B-6 B-7 B-8 B-O
Zero order R2 0.9727 0.9875 0.9893 0.9861 0.9975 0.9846 0.9740 0.9929 0.9911
First order R2 0.9869 0.9605 0.9773 0.9502 0.9322 0.9255 0.9879 0.9654 0.9627
Higuchi R2 0.6554 0.6767 0.6861 0.7501 0.7236 0.6879 0.6865 0.7657 0.7403
Korsmeyer- Peppas R2 0.9233 0.9746 0.9640 0.9752 0.9974 0.9885 0.9280 0.9767 0.9507
n 0.8470 0.9254 0.8825 0.8461 0.9282 0.9691 0.8115 0.8075 0.9727

R2 = squared correlation coefficients; n = diffusional exponent

CONCLUSION

In the current communication, gellan gum-linseed gum microbeads of aceclofenac were formulated via ionotropic gelation induced by Al3+-ions. These gellan gum-linseed gum microbeads of aceclofenac exhibited aceclofenac encapsulation efficiency of 27.70 ± 0.42 to 74.27±2.57 % and average sizes of gellan gum-linseed gum microbeads were ranged 739.57 ± 22.70 to 968.07 ± 42.24 µm. The gellan gum-linseed gum microbeads of aceclofenac demonstrated in vitro sustained release of aceclofenac over 8 h and this result could probably be important in terms of the potential medication advantages of favorable patient compliances and reduced dosing intervals. For this reason, these gellan gum-linseed gum microbeads of aceclofenac can be used as novel kinds of the potential option of polymeric microbeads carrier-matrices for sustained release of aceclofenac. The presented work showed an easy, economic and feasible approach to develop gellan gum-linseed gum microbeads for sustained release of aceclofenac via ionotropic gelation induced by Al3+-ions.

ACKNOWLEDGEMENT

The first author would like to acknowledge the Principal and Governing Body of Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, Mayurbhanj-757086, India.

FUNDING

Nil

AUTHORS CONTRIBUTIONS

All the authors have contributed equally.

CONFLICTS OF INTERESTS

The authors declare no conflict of interest.

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  8. Nayak AK, Hasnain MS. Okra gum-based multiple units for oral drug delivery. In: Nayak AK, Hasnain MS. Editors. Plant polysaccharides-based multiple-unit systems for oral drug delivery. Berlin: Springer; 2019. p. 83-92.

  9. Nayak AK, Ara TJ, Hasnain MS, Hoda N. Okra gum-alginate composites for controlled releasing drug delivery. In: Inamuddin AAM, Mohammad A. editors. Applications of nanocomposite materials in drug delivery, Woodhead Publishing Series in Biomaterials. United States: Elsevier Inc; 2018. p. 761-85.

  10. Nayak AK, Hasnain MS, Pal D. Gelled microparticles/beads of sterculia gum and tamarind gum for sustained drug release. In: Thakur VK, Thakur MK. Editors. Handbook of springer on polymeric gel. Singapore: Springer Nature; 2018. p. 361-414.

  11. Guru PR, Nayak AK, Sahu RK. Oil-entrapped sterculia gum-alginate buoyant systems of aceclofenac: development and in vitro evaluation. Colloids Surf B Biointerfaces. 2013;104:268-75. doi: 10.1016/j.colsurfb.2012.11.027, PMID 23334180.

  12. Nayak AK. Tamarind seed polysaccharide-based multiple-unit systems for sustained drug release. In: Kalia S, Averous L. editors. Biodegradable and bio-based polymers: environmental and biomedical applications, WILEY-Scrivener. USA; 2016. p. 471-94.

  13. Nayak AK, Pal D. Tamarind seed polysaccharide: an emerging excipient for pharmaceutical use. Indian J Pharm Educ Res. 2017;51(2s):s136-46. doi: 10.5530/ijper.51.2s.60.

  14. Nayak AK, Pal D. Functionalization of tamarind gum for drug delivery. In: Thakur VK, Thakur MK. Editors. Functional biopolymers. Berlin: Springer; 2018. p. 35-56.

  15. Hasnain MS, Rishishwar P, Rishishwar S, Ali S, Nayak AK. Extraction and characterization of cashew tree (Anacardium occidentale) gum; use in aceclofenac dental pastes. Int J Biol Macromol. 2018;116:1074-81. doi: 10.1016/ j.ijbiomac. 2018.05.133, PMID 29791876.

  16. Das B, Nayak AK, Nanda U. Topical gels of lidocaine HCl using cashew gum and Carbopol 940: preparation and in vitro skin permeation. Int J Biol Macromol. 2013;62:514-7. doi: 10.1016/j.ijbiomac.2013.09.049, PMID 24099938.

  17. Nayak AK, Hasnain MS. Fenugreek seed mucilage based multiple units for oral drug delivery. In: Nayak AK, Hasnain MS. Editors. Plant polysaccharides-based multiple-unit systems for oral drug delivery. Berlin: Springer; 2019. p. 93-112.

  18. Nayak AK, Pal D, Santra K. Screening of polysaccharides from tamarind, fenugreek and jackfruit seeds as pharmaceutical excipients. Int J Biol Macromol. 2015;79:756-60. doi: 10.1016/j.ijbiomac.2015.05.018, PMID 26007663.

  19. Maity S, Mahapatra SK. Formulation and evaluation of Al+3-induced gellan gum-Dillenia indica L. fruit gum-blended microbeads for sustained drug release. Int J Pharm Sci Res. 2021;12(2):1223-32.

  20. Hasnain MS, Guru PR, Rishishwar P, Ali S, Ansari MT, Nayak AK. Atenolol-releasing buccal patches made of Dillenia indica L. fruit gum: preparation and ex vivo evaluations. SN Appl Sci. 2020;2(1):57. doi: 10.1007/s42452-019-1756-x.

  21. Hasnain MS, Rishishwar P, Ali S, Nayak AK. Preparation and evaluation of aceclofenac dental pastes using Dillenia fruit gum for periodontitis treatment. SN Appl Sci. 2020;2(3):1-8. doi: 10.1007/s42452-020-2240-3.

  22. Saquib Hasnain MS, Rishishwar P, Rishishwar S, Ali S, Nayak AK. Isolation and characterization of Linum usitatisimum polysaccharide to prepare mucoadhesive beads of diclofenac sodium. Int J Biol Macromol. 2018;116:162-72. doi: 10.1016/j.ijbiomac.2018.04.151, PMID 29727643.

  23. Hasnain MS, Jameel E, Mohanta B, Dhara AK, Alkahtani S, Nayak AK. Alginates: sources, structure, and properties. In: Nayak AK, Hasnain MS. Editors. Alginates in drug delivery. United States: Academic Press, Elsevier Inc; 2020. p. 1-17.

  24. Hasnain MS, Ahmed SA, Alkahtani S, Milivojevic M, Kandar CC, Dhara AK, Nayak AK. Biopolymers for drug delivery. In: Nayak AK, Hasnain MS, editors Advanced biopolymeric systems for drug delivery. Berlin: Springer; 2020. p. 1-29.

  25. Hasnain MS, Nayak AK. Chitosan as responsive polymer for drug delivery applications. In: Makhlouf ASH, Abu-Thabit NY, editors, Stimuli-responsive polymeric nanocarriers for drug delivery applications. Vol. 1, Types and Triggers, Woodhead Publishing Series in Biomaterials. United States: Elsevier Ltd.; 2018. p. 581-605.

  26. Milivojevic M, Pajic Lijakovic I, Bugarski B, Nayak AK, Hasnain MS. Gellan gum in drug delivery applications. In: Hasnain MS, Nayak AK, editors, Natural Polysaccharides in Drug Delivery and Biomedical Applications. United States: Academic Press, Elsevier Inc; 2019. p. 145-86.

  27. Nayak AK, Hasnain MS, Dhara AK, Pal D. Plant polysaccharides in pharmaceutical applications. Adv Structured Mater. 2021;140:93-125. doi: 10.1007/978-3-030-54027-2_3.

  28. Maity M, Hasnain MS, Nayak AK, Aminabavi TM. Biomedical applications of polysaccharides, Tailor-Made Polysaccharides in Biomedical Applications. In: Nayak AK, Hasnain MS, Aminabhavi TM, editors. USA: Academic Press, Elsevier Inc; 2021. p. 1-34.

  29. Kandar CC, Hasnain MS, Nayak AK. Natural polymers as useful pharmaceutical excipients. In: Nayak AK, Pal K, Banerjee I, Maji S, Nanda U, editors, Advances and challenges in pharmaceutical technology: Materials. USA: Process Development and Drug Delivery Strategies Academic Press, Elsevier Inc; 2021. p. 1-44.

  30. Gorle AP, Mahale HV, Patil CS. Effective management of odontogenic infections through controlled fashion by a polymeric device containing moxyfloxacin. Int J Curr Pharm Res. 2017;9(5):100-6.

  31. Nayak AK, Pal D. Trigonella foenum-graecum L. seed mucilage-gellan mucoadhesive beads for controlled release of metformin HCl. Carbohydr Polym. 2014;107:31-40. doi: 10.1016/ j.carbpol.2014.02.031, PMID 24702915.

  32. Prajapati VD, Jani GK, Zala BS, Khutliwala TA. An insight into the emerging exopolysaccharide gellan gum as a novel polymer. Carbohydr Polym. 2013;93(2):670-8. doi: 10.1016/j.carbpol.2013.01.030, PMID 23499110.

  33. Nayak AK, Bera H, Hasnain MS, De A, Pal D, Samanta A. Gellan gum-based nanomaterials in drug delivery applications. In: Bera H, Hossain CM, Saha S, editors Biopolymer-based nanomaterials in drug delivery and biomedical applications. United States: Academic Press, Elsevier Inc; 2021. pp. 313-31.

  34. Nayak AK, Pal D, Santra K. Artocarpus heterophyllus L. seed starch-blended gellan gum mucoadhesive beads of metformin HCl. Int J Biol Macromol. 2014;65:329-39. doi: 10.1016/j.ijbiomac.2014.01.022, PMID 24447799.

  35. Nayak AK, Pal D, Santra K. Tamarind seed polysaccharide-gellan mucoadhesive beads for controlled release of metformin HCl. Carbohydr Polym. 2014;103:154-63. doi: 10.1016/ j.carbpol.2013.12.031, PMID 24528714.

  36. Nayak AK, Pal D. Plant-derived polymers: ionically gelled sustained drug release systems. In: Mishra M, editor M. (ed.) Encyclopedia of biomedical polymers and polymeric biomaterials. Vol. VIII. New York: Taylor & Francis; 2016. p. 6002-17.

  37. Rashid F, Ahmed Z, Hussain S, Huang JY, Ahmad A. Linum usitatissimum L. seeds: Flax gum extraction, physicochemical and functional characterization. Carbohydr Polym. 2019;215:29-38. doi: 10.1016/j.carbpol.2019.03.054, PMID 30981357.

  38. Nayak AK, Hasnain MS. Linseed polysaccharide-based multiple units for oral drug delivery. In: Nayak AK, Hasnain MS, (editors), Plant polysaccharides-based multiple-unit systems for oral drug delivery. Berlin: Springer, Singapore; 2019. p. 117-21.

  39. Safdar B, Zhihua P, Xinqi L, Jatoi MA, Rashid MT. Influence of different extraction techniques on recovery, purity, antioxidant activities, and microstructure of flaxseed gum. J Food Sci. 2020;85(10):3168-3182. doi: 10.1111/1750-3841.15426, PMID 32888361. 

  40. Safdar B, Pang Z, Liu X, Jatoi MA, Mehmood A, Rashid MT, Ali N, Naveed M. Flaxseed gum: extraction, bioactive composition, structural characterization, and its potential antioxidant activity. J Food Biochem. 2019;43(11):e13014. doi: 10.1111/jfbc.13014, PMID 31475377.

  41. Nerkar PP, Gattani S. In vivo, in vitro evaluation of linseed mucilage based buccal mucoadhesive microspheres of venlafaxine. Drug Deliv. 2011;18(2):111-21. doi: 10.3109/10717544.2010.520351, PMID 20954808.

  42. Basu S. Development and evaluation of a mucoadhesive nasal gel of midazolam prepared with linum usitatissimum l. seed mucilage. Sci Pharm. 2009. doi: 10.3797/scipharm.0807-10.

  43. Radha GV, Sastri KT, Prathyusha P, Bhanu P, Rajkumar J. Formulation and evaluation of aceclofenac proniosome loaded orabase for management of dental pain. Int J App Pharm. 2018;10(6):204-10. doi: 10.22159/ijap.2018v10i6.29143.

  44. Malakar J, Nayak AK, Pal D. Development of cloxacillin loaded multiple-unit alginate-based floating system by emulsion–gelation method. Int J Biol Macromol. 2012;50(1):138-47. doi: 10.1016/j.ijbiomac.2011.10.001, PMID 22020191.

  45. Malakar J, Nayak AK, Jana P, Pal DPal D, Jana P, Malakar J, Nayak A. Potato starch-blended alginate beads for prolonged release of tolbutamide: development by statistical optimization and in vitro characterization. Asian J Pharm. 2013;7(1):43-51. doi: 10.4103/0973-8398.110935.

  46. Nayak AK, Pal D, Hasnain MSSM. Development, optimization and in vitro-in vivo evaluation of pioglitazone-loaded jackfruit seed starch-alginate beads. Curr Drug Deliv. 2013;10(5):608-19. doi: 10.2174/1567201811310050012, PMID 23360248.

  47. Nayak AK, Pal D. Ionotropically-gelled mucoadhesive beads for oral metformin HCl delivery: formulation, optimization and antidiabetic evaluation. J Sci Ind Res. 2013;72:15-22.