INTRODUCTION:

Natural polymers have gained popularity in development of novel drug delivery systems in past a decade or so. They are preferred because they are biodegradable, readily available and possess ability for various types of chemical modifications. Aqueous solubility of natural excipients is very essential for designing modified release formulations. Various polymers have been investigated for the above purpose example sodium alginate, chitosan, tamarind gum and many others. One of the gums which is very less explored is okra gum(OG), okra gum is obtained from a plant know as Hibiscus Esculentus the fruits form the plant are source for the polymer, OG is a natural and plant derived polysaccharide composed of D-galactose, L-rhamnose, and L-galacturonic acid¹. Water is used for extraction and it gives a slimy and viscous solution. OG is chemically inert, biodegradable and biocompatible in nature². The highly viscous properties of OG have been utilized in formulation of sustained release systems^1,2.

Pellets are spherical small particles. They can be prepared from drugs, any excipients or granules and powders. These can be prepared by variety of processes^3,4. Compared to single unit dosage forms these pellets have some pharmacological and technological advantages like less side effects and dose dumping, enhanced bioavailability, good flow properties and ease of coating⁵.

Extrusion and spheronization is a process where wet dough is taken and extruded to form noodles like fragments, these fragments are further put into spheronizer to make spherical pellets. This process is a well established process that yields pellets of narrow size distribution and high drug loading⁶.

Various researchers have worked on preparation of pellets for the delivery of drugs like Ramipril, Mebeverine for extended release, some have worked on formulation variables which affect performance of pellets^7,8,9. Mucoadhesive microcapsules have been also researched upon¹⁰. Concept of mucoadhesion has also been investigated by preparing matrix tablets for oral and buccal absorption along with using natural sources like jack frui^11,12,13,14. Concept of mucoadhesion has also used by researchers to produce buccal patches¹⁵. Extrusion process has been extensively studied for providing controlled release form various dosage forms¹⁶.

In the present investigation the possibility of formulation of mucoadhesive pellets of OG have been tried by extrusion and spheronization process, as per the best knowledge of authors it has not been explored earlier. Metronidazole was chosen as a model drug for the preparation of the pellets. Metronidazole is one of the drugs which is useful in case of gastric ulcers caused by H.Pylori infection. Hence an attempt was made to formulate mucoadhesive pellets which will enhance the effect of the drug in upper GI tract.

MATERIALS AND METHODS:

Okra fruits were obtained from local market, Metronidazole was gift sample from Julphar Gulf Pharmaceutical Industries, Ras al Khaimah, UAE. All other ingredients used were of analytical grade.

Isolation of okra gum:

The method described by Priyanka et al¹⁷was followed with slight modifications. Okra fruits (pods) were washed and finely cut using a knife, the seeds were removed. The mass was mixed with distilled water and kept overnight. For filtration a muslin cloth was used. Acetone was added into the solution to precipitate the gum. Then, the precipitate was dried at 40^◦C. The dried film obtained was crushed and kept in tightly closed container.

Formulation of pellets:

Different formulations were prepared using various ratios of metronidazole, microcrystalline cellulose, okra gum and lactose. All the powders were thoroughly mixed and wet dough mass was prepared. The mass was fed manually into extruder (Shakti model EX-50/SSP120) fitted with a die/screen of 1mm diameter operated at a speed of 30rpm. Spheronization was carried out in a unit fitted with crosshatched plate. Spheronization speed was 750rpm and operated for 6 min.

Table 1: Formulation chart

Formu lation	Metronidazole (%)	Micro crystalline cellulose (MCC) (%)	Okra gum (%)	Lactose (%)
F1	10	35	2	53
F2	10	35	4	51
F3	20	40	6	34
F4	20	40	8	32

Characterization and evaluation of pellets:

Optical microscopy and average pellet size:

The pellets were observed employing Olympus microscope (Model BX 53) attached with DP 74 digital camera. The images were processed using cell sense software. In the cell sense software exposure time was adjusted to obtain the images.

The pellet size of different formulations was estimated by sieve analysis (Electrolab Model EMS 8). 50g of the sample was sieved employing a set of standard sieves. The sieve set was then mechanically shaken for 10 min. The net weight retained on each sieve was determined and these values were used for calculation of the average particle size.

Fourier-transform infrared (FTIR) spectroscopy:

The infrared spectroscopic analysis of metronidazole, okra gum and formulation was performed using Agilent Model Cary 630. The different spectra obtained are shown in figure 2.

Differential scanning calorimetry (DSC):

DSC studies were performed to find out any interaction between metronidazole and okra gum. The calorimeter (Shimadzu DSC 60+) was run at a scanning speed of 10°C/min. The temperature range of heating was 25–300°C. After sealing the samples in aluminum pans, heating was carried out in an inert atmosphere which was maintained by circulating nitrogen gas.

Friability:

The friability of the pellets was determined with a Roche friabilator operated for 10 min at 25rpm. For each study, 25g of pellets were mixed with 20 glass beads¹⁸.

Carr’s index and Hausner ratio:

50gm of the sample was put into a 100ml graduated cylinder and density apparatus (VTAP MATIC II). Bulk density, tapped density, Carr's index and Hausner ratio were calculated.

Angle of repose:

The angle of repose was measured according to the fixed funnel method.

In vitro drug release study:

It was done in 0.1 N HCl for 8 hrs using USP Dissolution Test Apparatus – Type I. The rotation was established at 50rpm and temperature was adjusted at 37 ± 0.2°C. Samples were withdrawn at different time intervals and absorbance was measured at λ 277nm by using UV spectrophotometer.

Samples were withdrawn at different intervals and absorbance was measured using UV spectrophotometer.

Swelling studies:

The swelling behavior of pellets was studied in 0.1 N HCl for 8 hrs. The pellets were soaked in the medium and swelled pellets were removed from the media and predetermined time intervals and after drying the surface of pellets using tissue paper, weight was noted¹⁷.

Weight of pellets after swelling- dry weight of pellets

Swelling index = -----------------------------------------------X 100

Dry weight of pellets

Mucoadhesion testing:

The mucoadhesive properties of pellets were evaluated by ex vivo wash off method, freshly excised piece of goat gastric mucosa were mounted on a glass slide in modified disintegration apparatus. About 50 pellets were spread onto the wet tissue specimen and was given a regular up and down movement. The study was done in 0.1 N HCl. The equipment was stopped at regular intervals and number of pellets still adhering to the specimen were counted¹⁷.

RESULTS AND DISCUSSION:

Optical microscopy and pellet size:

The surface morphology of the pellets were smooth and were spherical in nature. The size range was found to be in between 1540-1986 micrometer. It was observed that when the concentration of okra gum was increased the size of the pellets also increased this could be attributed to the higher concentration of gum which leads to more coherent mass and as a result, size of the pellets is increased.

Fourier-transform infrared (FTIR) spectroscopy:

The FTIR spectra of metronidazole, okra gum and formulation are shown in figure 2. The FTIR spectrum of metronidazole was characterized by principal absorption peaks at 1364.25 (NO stretching vibration), 3209.97 (N-H stretching vibration), 1182.51 cm^-1 (C-OH stretching vibration). The okra gum showed a peak at 1405.07 due to =C-H bend, a small peak at 1801.77 due to –C=O stretch, peak at 2928.91 due to C-H stretch and a broad band at 3384.70 cm^-1 due to –OH stretching vibrations. In the FTIR spectra of formulation various characteristic peaks of metronidazole and okra gum appeared without any significant deviations, hence it was concluded that there is no drug-excipient interaction.

Fig. 1: Images of formulation F1 and F2.

In vitro drug release study:

The in vitro drug release pattern is shown in figure 4. The drug release was found to decrease as the concentration of okra gum increased. This can be attribute to the swelling of the okra gum as the gum swells it forms a gel like structure through which diffusion of drug is less hence the drug release is controlled. This is in line with the data obtained for swelling studies. F1 and F2 showed around 90% of drug release within 8 hrs.

Figure 4. In vitro drug release of different formulations.

Swelling studies:

The overall swelling observed for all the formulations was not highly significant. It was in the range of 25.21- 44.31% for all the formulations.

The study showed that the pellets did not show greater swelling in 8 hrs in the gastric medium suggesting minimal or partial ionization of carboxyl group²⁰. As the concentration of okra gum was increased the swelling was found to be more this may be attributed to the gel like nature of gum which absorbs more water at higher concentrations leading to more swelling. This can be correlated to the drug release pattern which showed decrease as concentration of gum was increased.

Mucoadhesion testing:

All the three formulations showed good mucoadhesive strength at the end of 8hrs. As the concentration of the okra gum was increased it was found that the pellets adhered for more time in numbers to the mucosa. The study shows that the prepared pellets have good mucoadhesion and will retain the gastric fluid for drug release. The range was between 13.21- 21.29% at the end of 8hrs. The mucoadhesivity of the pellets could be ascribed to the presence of –OH groups of okra gum which form hydrogen bonds with the mucus molecules¹⁷.

CONCLUSION:

The current study proved that pellets can be successfully prepared by extrusion and spheronization using okra gum. From the current study it can be concluded that the okra gum pellets have good mucoadhesion and can be successfully used in the treatment of various conditions like gastric ulcer where the drug requirement is in the upper GIT.

ACKNOWLEDGEMENT:

The authors express their gratitude to the President of RAK Medical and Health Sciences University, UAE and Dean RAK College of Pharmaceutical Sciences for their encouragement and support in carrying out the research. The authors also thank Julphar, Gulf Pharmaceutical Industries, Ras Al Khaimah, UAE to provide gift sample of metronidazole.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

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Received on 27.07.2020 Modified on 10.09.2020

Research J. Pharm. and Tech. 2021; 14(6):3290-3294.

DOI: 10.52711/0974-360X.2021.00572

Formulation	Friability (%)	Carr index	Hausner ratio	Angle of repose
F1	0.47 ± 0.04	15.34 ± 0.23	1.17 ± 0.01	26.3 ± 0.15
F2	0. 37 ± 0.22	14.89 ± 1.11	1.08 ± 0.07	27.1 ± 0.19
F3	0. 43 ± 0.06	15.30 ± 0.77	1.06 ± 0.11	26.6 ± 0.22
F4	0.41± 0.03	15.23 ± 0.51	1.01 ± 0.31	26.1 ± 0.02