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The objective of the study was to evaluate banana powder as a superdisintegrant for the formulation of oral disintegrating tablets and to compare the results with commonly used superdisintegrants like croscarmellose sodium, pre gelatinised starch and sodium starch glycolate. Oral disintegrating tablets containing Domperidone as the model drug were formulated using five different concentrations of each superdisintegrant (2%, 4%, 6%, 8% & 10%) and compressed by direct compression. The formulations were subjected to various evaluation studies such as wetting time, water absorption ratio, disintegration time and in-vitro dissolution. The results showed that the disintegration time and drug release of the formulation containing banana powder (6%) was comparable to other super disintegrants. The IR spectrum analysis demonstrated that banana powder was compatible with the drug. These results suggest that banana powder can be used effectively as a superdisintegrant in orally disintegrating tablet formulations. Banana, is a natural product which is available in plenty, economically affordable and has its own nutritional value. It can be used as a potential additive in the formulation of oro -dispersible tablets.
Keyword: orodispersible tablets, superdisintegrants, disintegration time, natural excipients.
The tablet is the widely used dosage form because of its convenience in terms of selfâ€administration, compactness, and ease in manufacturing. For the past one decade, there has been a demand for more patientâ€friendly and compliant dosage forms. As a result, the development of new technologies has been increasing annually. Since the cost for development new drug molecule is very high, efforts are now being made by pharmaceutical companies to focus on the development of new drug dosage forms for existing drugs with more safety and efficacy together with reduced dosing frequency, and the production of more costâ€effective dosage forms.
However, geriatric and pediatric patients were having difficulty in swallowing conventional tablets, which leads to poor patient compliance. To overcome this problem, scientists have developed innovative drug delivery systems known as "melt in mouth" or "mouth dissolve (MD)" or sometimes "dispersible" tablets. These are novel types of tablets that disintegrate /disperse in saliva. Their characteristic advantages such as administration without water, lead to suitability for the geriatric and pediatric patients. They are also suitable for the bedridden patients, and patients who do not have easy access to water. The advantages, in terms of patient compliance, rapid onset of action, increased bioavailability (in some instances) and comparable stability to conventional tablets make these tablets popular as a dosage form of choice particularly in these populations.
Domperidone maleate is a widely used antiâ€emetic drug, acting by inhibition of the dopaminergic receptor. Domperidone maleate does not cross the blood brain barrier. Domperidone maleate is also effective in gastro paresis, pediatrics gastro esophageal reflux (infant vomiting). Domperidone maleate after oral dosing undergoes extensive gastric and hepatic first pass metabolism resulting in low bioavailability (15%) which therefore, may not minimize the rate of vomiting. In context of the above principles, a strong need was recognized for the development of mouth dissolving tablets of Domperidone maleate to improve its bioavailability for relief on nausea and vomiting.
In mouth dissolving tablets, disintegrants plays a major role. A disintegrant is a substance in a tablet formulation that enables the tablet to break up into smaller fragments upon contact with gastrointestinal fluids. Such a rapid rupture of the tablet matrix increases the surface area of the tablet particles, thereby increasing the rate of absorption of the active ingredient and decreasing the onset of time to therapeutic effect. A new disintegrant class has emerged during the recent past known as the Superdisintegrant. Superdisintegrants improve disintegrant efficiency resulting in decreased use levels, typically 1-10% by weight relative to total weight of tablet when compared to traditional disintegrants.
The excipients added to the formulation should not only act as formulating agent it also act as good therapeutic agent and also free from toxicity. In the present research work an attempt was made to use banana powder as a superdisintegrant in the formulation of mouth dissolving tablets. Banana powder being a natural substance and rich in nutrition and availability can be an added advantage in using them as a pharmaceutical excipient.
MATERIALS AND METHODS
Domperidone maleate was a gift from sterling lab(hosur,India) banana powder(self made) croscarmellose sodium(CCS) and sodium starch glycolate(SSG)as pharmaceutical grade was obtained from Loba chem ,mumbai, pre-gelatinised starch(PGS) as pharmaceutical grade was obtained from colorcon, Mumbai ,all other materials used were of suitable analytical grade.
Preparation of banana powder:
The unriped banana fruit was purchased from the local market. The fruit was cleaned and the peel was removed. Then the pulp was dried and powdered using mixer. The powdered substance was collected and stored in well closed container for further studies.
Phase solubility studies:
Phase solubility studies was done as per the method reported by (K.Venkates et.al,2009)2.Drug and superdisintegrant as per specified ratio(1:1,1:2,1:3,1:4,1:5) were weighed accurately and added to 25ml of water in screw capped bottles. All the bottles were shaken in Remi orbital incubator shaker at 370c with 100rpm for 24 hr. The container with drug and water was used as control. After 24 hr the solution was filtered using whatman filter paper (0.45 microns) .Then the filtrate was analyzed at wavelength of 284nm using Systronics TM double beam spectrophotometer. From the absorbance the solubility of drug was calculated.
The compatibility study of drug with excipients was done using IR spectroscopy. The drug and the excipients were mixed in a ratio of 1:1 and stored in glass vials at 40°C/75% RH for 30days. At the end of 30 days samples were withdrawn from each vial and the IR spectrum for those samples were taken. The samples were prepared by pressed pellet technique. The IR spectra's was determined using JASCO FT/IR-4100(3-4).16 scans were taken for each sample. The scanning range was between 4000-400 cm-1. The IR spectra of pure drug and pure excipients were compared to that of the mixture of drug and excipients and any interaction were analyzed.
Microbial load for banana powder:
Pour plate method was used to cultivate 1ml of banana powder solution with distilled water on muller Hilton agar medium for enumeration of bacteria and sarboured dextrose agar medium for fungi. The plate was incubated at 370c for 24 hours for bacteria while fungi plates were incubated at 270c for 72 hrs (3-6). At the end of the incubation period, the bacterial and fungal colonies formed were counted. Sterilized banana powder solution was taken as control.
Swelling index was defined as the volume in milliliters occupied by 1 gram of superdisintegrant powder including any adhering mucilage, after it had swollen in water for 4 hour. The swelling index of the superdisintegrant was performed according to the (BP, 2007) method (7-9). In a 25ml ground- glass stoppered cyclinder graduated over a height of 125±5 mm in 0.5 ml divisions. About 25ml of water was added and shaken vigorously every 10 min for 1 hour and then allowed to stand for 3 hours. The volume occupied by the superdisintegrating agent including adhering mucilage was measured. The swelling index was calculated from the mean of three determinations.
All materials were mixed as per the composition shown in table1 and passed through 60 mesh sieve. The pre-compression studies (10-11) were done as follows.
It is the ratio of total mass of powder to the bulk volume of powder. It was measured by
Pouring the weight powder (passed through standard sieve # 60) into a measuring cylinder and initial weight was noted. The initial volume is called the bulk volume. From this the bulk density is calculated according to the formula. It is expressed in g/ml and the equation was given by
Bulk density= mass/bulk volume (1)
It is the ratio of total mass of the powder to the tapped volume of the powder. Volume was
Measured by tapping the powder for 750 times and the tapped volume was noted if the difference between these two volumes is less than 2%. If it is more than 2%, tapping is continued for 1250 times and tapped volume was noted. Tapping was continued until the difference between successive volumes is less than 2 % (in a bulk density apparatus). It is expressed in g/ml and the equation was given by
Tapped density= mass/ tapped volume. (2)
Carr's index (or) % compressibility:
It indicates powder flow properties. It is expressed in percentage and is given as
Carr's index =Tapped density-Bulk density/Tapped density (3)
Hausner ratio is an indirect index of ease of powder flow. It is calculated by the formula given below.
Hausner ratio= Tapped density/bulk density (4)
Lower hausner ratio (<1.25) indicates better flow properties than higher ones (>1.25).
Preparation of tablet:
All the materials were passed through 60 # screens prior to mixing. Domperidone maleate, Croscarmellose sodium (CCS), Sodium Starch Glycolate (SSG), Pre-gelatinised starch(PGS),Banana powder, Microcrystalline cellulose(MCC),Neotame(nutrasweet), Mannitol(DC) , Talc, Magnesium stereate and flavour ( pharmaceutical grade) were mixed using a glass mortar and pestle. The formulation without superdisintegrant was prepared and used as control. All the materials were directly compressed into tablets using concave face round tooling on a Rimekâ€ rotary tablet machine at 12 rpm . The composition of the batches is shown in Table 1.
Table1: Formulation of mouth dissolving tablet.
Evaluation of tablet:
The hardness of the tablet was determined by using Tab machine hardness tester.
Twenty tablets were selected randomly from each formulation and weighed individually using a Shimadzu digital balance (BL-220H). The individual weight was compared with the average weight for the weight variation.
The friability of the tablets was measured in a Friability apparatus (Campâ€bell Electronics, Mumbai). Tablets of a known weight (W0) or a sample of 20 tablets are dedusted in a drum for a fixed time (100 revolutions) and weighed (W) again. Percentage friability for each formulation was calculated from the loss in weight as given in equation below. Determination was made in triplicate.
% Friability = W0â€’WÃ-100/ W0 (5)
A piece of tissue paper folded twice was placed in a small petridish (internal diameter = 6.5 cm) containing 6 ml of simulated saliva pH (phosphate buffer pH 6.8). A tablet was placed on the paper, and the time required for complete wetting was measured visually. Six measurements were performed for each batch (Nitin Jonwal et al, 2010).
Water absorption time:
A piece of tissue paper folded twice was placed in a small petridish (Internal Diameter = 6.5 cm) which containing 6 ml of phosphate buffer (pH6.8). A tablet was placed on the paper and the time required for complete wetting was then measured (Nitin Jonwal et al, 2010). The water absorption ratio (R) for the each formulation was determined using the following Equation.
Water absorption ratio (R) =Waâ€’ Wb Ã-100 / wb (6)
Where, Wb is the weight of the tablet before water absorption and
Wa is the weight of the tablet after water absorption.
Disintegration test was done by using disintegration apparatus(camp-bell electronics, Mumbai)with distilled water as disintegration media at 370c and the time in second taken for complete disintegration of tablet with no palpable mass in the apparatus was noted visually (Nitin Jonwal et al,2010).
In-vitro dissolution study:
The release study was performed using(Tab machine) six stage dissolution rate apparatus (BP/IP/USP) paddle type with 900ml of 0.1N HCL(PH=1.2) as dissolution medium at 370c and 50rpm. The sample10ml was withdrawn with the time interval of 1, 2, 3, 4, 5, 10, 15, 20,25and 30 min. The volume of withdrawn sample was replaced with 10ml 0.1N HCL. The sample was filtered. Absorbance of the sample was measured using PC Based double beam spectrophotometer. The cumulative release was measured using equation obtained from standard curve. The regression co efficient of the standard was R2= 0.9997.
RESULTS AND DISCUSSION:
Phase solubility studies:
The phase solubility studies was done as per the method reported by K .Venkates etal2.The solubility of drug was determined by increasing the concentration of superdisintegrant by specified ratio(1:1,1:2,1:3,1:4,1:5). The pure drug had a solubility of 0.2mg/ml whereas the solubility of the drug with added superdisintegrants showed a value of about 0.44 to 1.1mg/ml for CCS, 0.46 to 1.21mg/ml for SSG, 0.34 to 0.46mg/ml for PGS and 0.8 to 2.7mg/ml for banana powder. The above results suggested that on increasing concentration of the superdisintegrants the solubility of the pure drug tends to increase. Of the four superdistegrants used, banana powder showed the maximum increase in solubility of the drug.
Conc. of superdisintegrant
*avg for three replicates±SD
Table 2: Phase solubility studies
The drug excipient compatibility study was done by using JASCO FT/IR spectrometer. The IR spectra for pure drug, excipients and drug-excipient mixture were shown in Figure1. The pure drug showed characteristic absorption bands at 3127.97(Aromatic CH stretching), 1487.81(C=C ring stretching), 1147.44(CH2 Alkane bending), 928.557(RCH=CH2), 891,866,833(Para substituted benzene) and the formulation shows characteristic absorption band at 3123.15(Aromatic CH stretching), 1487.81(C=C ring stretching), 1147.44(CH2 Alkane bending), 928.557(RCH=CH2), 891,865,833(Para substituted benzene). The spectrum of the drug-excipient mixture was found to be a mere summation of the individual spectrum of the drug and excipients which suggest that there were no interaction between drug and excipients and were compatible with each other.
Figure 1: Compatibility studies.
The swelling indeces for the crosscarmellose sodium, sodium starch glycolate , pre-gelatinised starch, banana powder are presented in table3. The values obtained suggest that the swelling index banana powder is comparable to other superdisintegrant.
The banana powder was a natural substance and so the microbial load test was done and the results shown that it contains microbial growth of about 253 cfu/gm and fungal growth of about 89 cfu/gm which was under the limit specified by (United state pharmacopoeia,2007)(5).
All the materials was mixed as per composition shown in table1.For each designed formulation blend of drug and excipients was prepared and evaluated for micromeritic properties and the obtained results were shown in Table3. The bulk density and tapped density for all formulation was presented in table 3. The hausners ratio and %compressibility index was found to be in the range of 1.14-1.28 and12-22% (Table 3). All formulation shows good blend property for direct compression and hence tablet was prepared by using direct compression technology. The results shows that formulation containing banana powder has better physical properties compare to other formulation (Table 3).
Bulk density gm/cm3
Tapped density gm/cm3
Cross carmellose sodium
Sodium starch glycolate
Table 3: Pre-formulation studies.
Evaluation of tablets:
The tablet was prepared by direct compression method as per Table1.The prepared tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, as shown in Table4. The weight variation was found to be in the range of 248mg-253mg for all formulation .The hardness was found to be in the range of 2-3kg/cm in all formulation indicating good mechanical strength and it has ability to with stand physical and mechanical stress condition while handling. The friability for all formulation was less than 1% as per (British pharmacopoeia, 2007) .
The wetting time is closely related to the inner structure of the tablet. This method mimics the action of saliva in contact with the tablet to illustrate the water uptake and subsequent wetting of tablet. This shows the wetting process was very rapid in almost all formulation. This may be due to the ability of swelling followed by breaking and also capacity of water absorption and swelling. The wetting time was found in the range of (Table4). Water absorption which is important criteria for understanding the capacity of disintegrants to swell in the presence of light amount of water was calculated. The tablets showed in the range of 12-100 sec (Table4). This shows all the formulation have good water absorption capacity.
Water absorption ratio
Sodium starch glycolate(S1-S5)
Table 4: Evaluation of mouth dissolving tablets
The most important parameter that needs to optimize in the development of mouth dissolving tablet is the disintegration time of tablet. In the present study all the formulations disintegrated within 1min. Table 5 give the disintegration time achieved by all the formulation. Four replicates were done. The disintegration time for tablet prepared with banana powder was much lower than the other synthetic superdisintegrants, indicating that banana powder has good disintegrant property (Table 5). Among the synthetic agents CCS was found to be having good disintegrating property than SSG and PGS. This rapid disintegration of banana powder and CCS was due to their rapid capillary activity and pronounced hydration with little tendency to gel formation . The results are in consistent with wetting and water absorption time.
Disintegration time for all formulation*
Sodium starch glycolate
*Avg of six replicates ±SD
Table 5: Disintegration time for prepared mouth dissolving tablet.
The drug release studies of the prepared formulations were done as per the method prescribed by British pharmacopoeia. The dissolution profiles of all the formulations were shown in Figure 2-6. It is clearly evident from the obtained data, that the tablet with banana powder as superdisintegrant showed excellent drug release as compared to other agents. It is clear that release of drug has improved considerably in formulation containing banana powder and CCS due to the rapid capillary activity and pronounced hydration with little tendency to gel formation. But the formulation containing SSG and PGS has less dissolution efficiency because it has more tendencies to form gel formation .The batch B3 containing banana powder (6%) and C3 containing CCS (6%) shows good dissolution efficiency and rapid dissolution compare to SSG and PGS.
Percentage Drug release of 2% concentration of superdisintegrant*
*Avg of two replicates ±SD
Table 6: In-vitro release profile of 2% concentration of superdisintegrants.
Figure2: In-vitro drug release of formulation at 2% concentration of different superdisintegrants.
Percentage Drug release of 4% concentration of superdisintegrant*
*Avg of two replicates ±SD
Table 7: In-vitro release profile of 4% concentration of superdisintegrants.
Figure3: In-vitro drug release of formulation at 4% concentration of different superdisintegrants.
Percentage Drug release of 6% concentration of superdisintegrant*
*Avg of two replicates ±SD
Table 7: In-vitro release profile of 6% concentration of superdisintegrants.
Figure4: In-vitro drug release of formulation at 6% concentration of different superdisintegrants.
Drug release of 8% concentration of superdisintegrant
*Avg of two replicates ±SD
Table 8: In-vitro release profile of 8% concentration of superdisintegrants.
Figure 5: In-vitro drug release of formulation at 8% concentration of different superdisintegrants
Drug release of 10% concentration of superdisintegrant
*Avg of two replicates ±SD
Table 8: In-vitro release profile of 10% concentration of superdisintegrants
Figure 6: In-vitro drug release of formulation at 10% concentration of different superdisintegrants
The present study was aimed at evaluating the disintegrant property of banana powder in the formulation of mouth dissolving tablets. The obtained results clearly demonstrate the ability of banana powder as a superdisintegrant. The disintegration time obtained by tablets with banana powder wascomparable to that obtained with other commonly used disintegrants. Hence it can be used very effectively in the formulation of MDTs. Banana powder being a natural product with abundant availability can be used as a potential pharmaceutical excipient in various solid dosage forms especially in fast release products. The economical and nutritional value of banana powder will be an added advantage of using them in the pharmaceutical formulations.