INTRODUCTION:

Excipients are inactive additives, used to make up an effective pharmaceutical dosage. This include fillers, binders, flavors, dyes etc. Among them, binders are important pharmaceutical excipients that are usually used in formulation of tablet to induce cohesion on the powder mix and improve on the flow properties of the granules¹. The subsequent aggregation confirms that the tablet remains intact even after compression². Binders can function as adhesives by agglomerating powder particles together hence converting them to granules by wet granulation process. These granules are compressible and free-flowing.

This type of excipients are appropriate for formulations of tablets with low or high concentration of soluble or insoluble medicaments. In drug delivery system, binders with polymeric chemistry highly suitable for sustained release of drugs. There are several factors influencing on the drug release properties such as physicochemical nature of the polymers, dosage levels, ratio of polymer and drugs^3,4. However, commonly synthetic and semi-synthetic binders are used for tablet formulation, but they might have some side effects. Thus there is always demand of natural polymers as adhesives, binding agents which are natural origin, less toxic, cost-effective and environmentally safe. Plant-based waste as biopolymer is the best substitute among the all the binding agent like starch, gelatin, natural gums, acacia sodium alginate, methyl-cellulose, microcrystalline cellulose due to its easy availability and bio-degradability^5-7.

Corn cob is a major part of the corn’s waste. It is estimated that 40-50% of corn is corn cob. Corn cob consist of 35.5% fiber, 2.5% protein, 0.12% calcium and 0.04% phosphorus. The corn cob’s fiber contains of 30-40% cellulose, 20-36% hemicelluloses, 16% lignin and 8% other materials. The hemicelluloses can be utilized as a new alternative polymer for various applications especially in pharmaceutical preparations⁸. Manilkara zapota (L.) P. Royen, commonly known as Sapodilla, chickoo or sapota, one of the wonders of nature belongs to family Sapotaceae including about 65 genera and 800 species. The seeds contain some phytochemicals like achras saponin and the bitter sapotinine. These phytoconstituents produced in the seeds and other plant parts of sapodilla are responsible for their antioxidant activities and pharmacological applications⁹. The aim of present work is to extract hemicellulose from corn cob and mucilage from sapota seed and used as binding agent with standard model drug Cefpodoxime proxetil.

MATERIALS AND METHODS:

Materials and chemicals:

Raw materials for the preparation of natural polymer namely corn cob and sapota seeds were collected from local area near Tambaram, Chennai. Other chemicals used were of analytical grade and were used without further purification.

Isolation of hemicelluloses from corn cobs:

The corn cobs (CC) powder of 50gm was added to 500 cm³ of 0.1M NaOH in 70% ethanol and heated at 60°C, then stirred for 2 h to dissolve the lignin. The suspension was allowed to cool to room temperature and filtered through Whatman filter paper. The precipitate was added 500 cm³ of 0.2 M NaOH and stirred for 8 hours at room temperature to dissolve hemicelluloses, and then filtered. The filtrate was heated at a temperature of 65°C, and added 137 cm³ of 3% H₂O₂ in stages. Each addition of 1 cm³ 3% H₂O₂to the filtrate was stirred constantly. Stirring was performed until the entire 3% of H₂O₂ was used and continued to a clear solution. Solution of 10% acetic acid in 95% ethanol with a ratio of 1:4 (v/v) was added to the sample solution and left at room temperature for 6 h until the precipitate was formed. The suspension was centrifuged at a rate of 10,000 rpm for 15 min, and the filtrate was discarded. The hemicellulose precipitate was washed with 96% ethanol, and dried in vacuum dryer¹⁰.

Isolation of mucilage from sapota seeds:

Mucilage was isolated from the sapota seeds (SS) using maceration techniques in which seed powder (100g) was soaked in cold distilled water (500mL) and slurry was prepared. Then slurry was kept aside for a day, then solution was heated on Bunsen burner for 1h; after one day the mixture was filtered with the help of muslin cloth. The filtrate was centrifuged at 3000rpm for 10 min. The supernatant was collected after centrifugation then double volume of acetone was added in it to precipitate the mucilage. The precipitate was washed with chloroform. The mucilage was then dried at 40℃–45℃ in hot-air oven and then passed through mesh number 120 and stored in desiccators until used for further studies in powder form. Deionized water was used for all experiments¹¹.

Characterization of materials:

The biopolymers extracted from corn cobs and sapota seeds was characterized by FTIR analysis. FTIR spectra were recorded in the scanning range was from 4000 to 400 cm⁻¹ and the resolution was 1 cm⁻¹on FTIR.

Preparation of tablets by using wet granulation methods:

Two different batches of tablets were prepared using wet granulation technique. The composition of single tablet per batch is given in Table 1. Each polymer was used separately. The amount was calculated that required to prepare 100mg cefpodoxime proxetil tablets containing drug and binder and mixed uniformly. A proper amount of distilled water was added slowly to prepare wet mass. The compressed tablets of each batch were stored in air tight container.

Table 1: Formulation of tablets using natural polymer corn cobs (CC) and sapota seed (SS)

Ingredients	CC		SS
Ingredients	T1	T2	T3	T4
Drug (mg)	50	10	50	10
Natural polymers (mg)	50	90	50	90

Evaluation of the formulation^12-15:

The prepared formulations were evaluated for the following parameters:

Pre-compression evaluation:

Angle of repose:

The accurately weight granules were taken in the funnel. The granules were allowed to flow through the funnel freely on to the surface. The diameter of the granules cone was measured and angle of repose was calculated using the following equation:

tan θ = h/ r or θ = tan^-1 (h/ r)

Where;

θ = angle of repose,

h = height of the cone, and r = radius of the cone base

Bulk density:

Bulk density (D_b) was determined by measuring the volume (V_b) of known weighed quantity (W) of granules using bulk density apparatus and can be calculated by using the formula:

D_b = W/ V_b

Tapped density:

Tapped density (Dt) was determined by measuring the volume (V_t) of known weighed quantity (W) of granules using bulk density apparatus and can be calculated by using the formula:

D_t = W/ V_t

Carr’s Index:

The Carr’s index (% compressibility) of the granules was calculated from the difference between the tapped and bulk densities divided by the tapped density and the ratio expressed as a percentage.

Carr’s Index (%) = D_t – D_b/D_t X 100

Where, D_t is the tapped density and D_b is the bulk density.

Hausner’s Index:

The Hausner’s index was calculated by dividing the tapped density by the bulk density of the granules.

Hausner’s index = D_t/ D_b

Where, D_t is the tapped density and D_b is the bulk density.

Post-compression evaluation:

Tablet Thickness:

The thickness of the tablets was determined by using screw gauge. Five tablets were used, and average values were calculated.

Content Uniformity:

The content uniformity of the tablets was performed by weighing the tablets and crushing them. Then they are dissolved in 100 mL water to prepare the stock solution. From the stock solution 1mL is taken and it is diluted with 0.1N HCL. The tablets are then dissolved and OD value is noted in the frequent interval of 30 min in UV-visible spectrophotometer. The drug content was estimated from the standard curve of cefpodoxime proxetil.

In-vitro drug release study:

The in vitro drug release test was carried out at a constant temperature of 37 ± 0.05°C using a rotating basket apparatus method rotated at 100 rpm. About 300 ml of phosphate buffer solution (pH 7.4 and 1.2) was used as the dissolution media to stimulate gastrointestinal tract (GIT) conditions. A 2ml aliquot was used each time for analyzing cefpodoxime proxetil at a fixed time interval (30 min). The amount of drug released was analyzed using a UV-vis spectrophotometer at 260nm and the drug release at different pH is determined in order to know the drug release capacity of the binder.

RESULTS AND DISCUSSION:

Formation of tablet:

Drug- binder interactions play a crucial role with respect to release of drug in proper rate and amount. Here hemicelluloses from corn cob and mucilage from sapota seeds, were extracted and was used as natural binders (Figure 1). Here tablets were prepared and verified by several pre-compression and post-compression methods.

Fig 1: a) Corn cob, b) extracted hemicellulose powder from corn cobs, c) sapota seed and d) extracted mucilage from sapota seeds

Characterization of natural polymer by FTIR:

Figure 2a shows the FTIR spectrum of hemicellulose extracted from corn cobs. The strong IR peaks at 1001, 1403, and 3465 cm^–1 corresponds to stretching vibration of C–OH bond, methylene scissoring vibrations, and free O–H vibrations, respectively. The medium intense band at 1653, 1784 cm^–1 are ascribed to sp² hybridized C=C carbon bond vibration, C=O in –COOH groups, respectively. Minor peak observed at 2925 cm^–1 are due to symmetric stretching vibrations of C–H bond¹⁶. All the absorption band depicts that hemicellulose successfully extracted from corn cobs.

Fig 2: FTIR spectra of a) corn cob hemicellulose and b) sapota seed mucilage

Figure 2b displays several distinct peaks of sapota seed positioned at 1002, 1421, 1595, 2921, and 3261 cm^–1 which conform that mucilage is successfully extracted from seeds. Two strong, intense bands appeared at around 1002, 1595 and 3261cm^–1 are attributed to stretching vibration of C–OH bond, sp² hybridized C=C carbon bond vibration, and free O–H vibrations, respectively. Few less absorption bands located at 1421, and 2921 cm^–1 are ascribed to methylene scissoring vibrations and symmetric stretching vibrations of C–H bond, respectively¹⁷.

Pre compression parameters:

The prepared different formulations were assessed for pre-compression parameters and their results were given in Table 2. The hemicellulose obtained from corn cobs and the mucilage from sapota seeds were evaluated for various parameters like angle of repose, bulk density, tapped density, Carr’s index and Hausner’s index. Angle of repose has been used to characterize the flow properties of solids. It is a distinct feature that related to inter particulate resistance or frictional movement between particles. The angle of repose determines flow properties of solids. When the angle of repose is less than 25°, the flow is said to be outstanding and more than 40°, the flow is considered to be poor. In our study, angle of repose values are 1.831 and 1.273 for hemicelluloses and mucilage, powders respectively, which depicts its excellent flowing characteristics. Bulk density is an essential parameter for process development and solid dosage manufacturing. It is the weight of particles in a given volume under the influence of gravity or unsettled apparent volume. It is used in determining the amount of powder that can fit in a space such as a blender or a hopper on a tablet press or capsule filler. It influence the bulking properties of powder and also the interactions that interfere with powder flow. It also directly related with porosity. Result of bulk density was obtained as 0.16g/cm³ and 0.21g/cm³ for hemicellulose and mucilage powder, respectively. Tapped density is the maximum packing density of the powder achieved under the influence of well defined, externally applied forces. The minimum packed volume achieved depends on a number of factors including particle size distribution, true density, particle shape and cohesiveness due to surface forces including moisture. It can be used to predict both the flow properties and the compressibility. Here tapped density are found to be 0.31g/cm³ and 0.35g/cm³for hemicellulose and mucilage powder, respectively. The Carr’s index and Hausner’s index can be used as an index for the flowability of a powder because the densification occurring during tapped density measurement is influenced by the same inter-particulate interactions which are affecting the flow of powders. Carr’s index can be defined as the change of volume of the powder under a normal pressure and is an indicator of flowability. The greater the compressibility of a particulate solid, the lower its ability to flow. A powder having a compressibility index lesser than 20% is considered to have good flowability. From the bulk and tapped density values, the Hausner index (HI) is also determined. The higher the Hausner index value, the lower the flowability of the powder. If the HI is greater than 1.4 the powder is considered cohesive and therefore has problems in flowing; a HI lower than 1.25 characterizes a free flowing powder. The values of Carr’s index are 18.3 and 19.4, Hausner’s index are 1.13 and 1.15 for hemicellulose and mucilage powder, respectively. Resulting features for pre-compression parameters depicts that both the biopolymers apt as an excellent binder agent with high flowability and good compressibility properties.

Table 2: Evaluation of pre-compression parameters

Parameter	Corn cob powder	Sapota seed powder
Angle of repose	1.831	1.273
Bulk density	0.16	0.21
Tapped density	0.31	0.35
Carr’s index	18.3	19.4
Hausner’s index	1.13	1.15

Post compression parameters:

The prepared tablets were evaluated for post-compression parameters such as thickness, content uniformity and in-vitro drug release profile characteristics. Table 3 shows the results of the evaluation tests of tablet thickness, content uniformity of corn cob hemicellulose and sapota seed mucilage with the model drug. All the formulations of tablets with natural polymer showed very slight thickness variation and it ranged from 0.9 to 1.1cm. Thickness values increase with higher content of polymers for both cases. The content uniformity was obtained between 0.042 - 0.0.918, where lower the biopolymer content, higher the absorbance and vice versa.

Table 3: Determination of post-compression parameters

Parameter	T1	T2	T3	T4
Thickness (cm)	0.9	1.6	0.8	1.1
Content uniformity	0.917	0.042	0.918	0.048

In-vitro drug release profile:

In-vitro release profile of the drug from tablets was major governing criteria to decide whether the natural binder or the commercially used binder is good binding agent. The release profile for the drug was taken for a period of five hours which can best be depicted by graph between percentage drug release and time. Phosphate buffer solution (pH 7.4 and 1.2) was used as the dissolution media or drug release study to simulate gastrointestinal tract (GIT) conditions¹⁸. (Merina Paul das et al., 2016).

The in-vitro dissolution profiles of the prepared formulations of tablets with biopolymers extracted from sapota seeds and corn cob were shown in Figure 3a (pH 7.4) and Figure 3b (pH 1.2). T4 formulation showed maximum release of 83.56 % at pH 7.4, and 96.36 % at pH 1.2, at 270 min. The drug was released in the dissolution media slowly with the time; this sustained effect cause prolonged treatment by the drug. The drug release is shown better results in T4, at pH 7.4, as it gradually increases in % release. While, in pH 1.2, all the four formulations give nearby values of % drug release. In both pH, higher amount of biopolymer produced better drug release profile than the lower content. Hemicellulose from corn cob and mucilage from sapota seed at T2 and T4 formulations exhibited an outstanding results as drug binder compared to T1 and T3 composition, respectively.

CONCLUSION:

The preparation of tablet formed with natural polymer hemicelluloses of corn cob and mucilage of sapota seeds and drug like cefpodoxime proxetil to formulate oral controlled release tablets exhibited appropriate compression. Based on the different compression test, a major conclusion can be made that corn cob hemicellulose and sapota seeds mucilage which are natural polymer, has enormous potential to substitute the commercially existing synthetic excipients used as binders in tablet dosage forms. Higher quantities of polymer showed better controlled drug release pattern from the formulations using lower content. It was also found that biopolymers are pH-sensitive, so these binders can be used to formulate different oral drugs for effective gastrointestinal delivery system to achieve desired therapeutic effect.

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Received on 03.07.2019 Modified on 08.08.2019

Research J. Pharm. and Tech 2020; 13(2):669-673.

DOI: 10.5958/0974-360X.2020.00128.6