Formulation and in vivo evaluation of oro-dispersible tablets of ayurvedic powders Sitopaladi and Talisadi

Deepak Khobragade, Sunil Kumar, Arun Kotha, Richa Gupta, K. Ravalika

Vijaya College of Pharmacy, Hyderabad-501 511, Telangana, India

*Corresponding Author E-mail: ksdeepak31@gmail.com

ABSTRACT:

Most of the ayurvedic medicines are in the form of powder and they may have some kind of unacceptable or bitter taste and have problem of patient compliance. Medicines in powder form have problem of administration of accurate dose with ease. Furthermore it needs water or honey for administration and chances of spoilage and waste are more. Formulation of Oro-dispersible tablets which rapidly disintegrate in mouth will be the best remedy for efficient use of ayurvedic powders. The aim of this study was to formulate oro-dispersible tablets of ayurvedic polyherbal powder Sitopaladi and Talisadi using various excipients like super-disintegrants and sweeteners and compare the efficacy in vivo using rats. The cough suppressing activities of powder and tablets was evaluated by counting bouts of cough in control group and treated group rats with powders and ODT. Codeine was taken as standard anti-tussive drug for our research. The cough bouts were produced in rats by exposure to SO₂generated by reaction of Na₂SO₃ and water in a Desiccator. The test results show that there is very little change in the activity of formulated tablets and pure ayurvedic powder. Thus it can be concluded from the study that that formulation of oro-dispersible tablets of ayurvedic powder preparation not only results in improving acceptability, ease and accuracy of administration without affecting efficiency of powder ayurvedic preparations like Talisadi and Sitopaladi.

KEYWORDS: Talisadi, oro-dispersible, ayurvedic, poly-herbal powder, cough.

1. INTRODUCTION:

Ayurvedic medicines are somewhat less popular because most of the drugs are in powder form and are generally prepared from natural ingredients which may have some specific unacceptable taste. These Ayurvedic powders are taken 1-1/2 teaspoon along with honey and or water because of the problem in administrating powder as such and unpalatable taste. This leads to decrease in patient compliance^1,2. Powders have also problem of administration of accurate dosage and with ease due to their fine particulate nature. There are chances of spilling and spoiling and spreading all over with powder formulations especially bulk powders.

So to avoid the drug adherence issue, carrying drug and honey, and various other disadvantages which arise due to powder nature of ayurvedic formulation, there is a need to convert these powders formulations into suitable modern dosage form.

Solid formulations like tablets and capsules, mostly administered by oral route are mostly preferred by manufacturers, prescribers and patients. These formulations are most popular of convenience in administration of drug and patient compliance. But because of unpalatable taste of drugs and difficulty in administration and swallowing in case of geriatric, pediatric, bed ridden patients, the drug cannot be given as such in oral conventional formulations may it be tablet or capsule. To overcome this, a new approach i.e. development of mouth dissolving/dispersing solid formulations have generated a lot of research interest^3,4.

Oro-dispersible⁵ tablets are one of the kind of formulations which have sufficient hardness, fast disintegration rate and pleasant taste ^6,7,8. These tablets get disintegrated in the saliva and dissolve^9,10,11 These tablets are formulated with special type of excipient called super disintegrants to aid rapid disintegration, sweetening agent to mask the bitter taste, making it palatable and flavoring agent to leave a pleasant taste and feel in the mouth. In these formulations, some of the drug gets absorbed through pharynx and esophagus while it is travelling to the stomach thus increasing the bioavailability and making it more beneficial than other conventional tablet dosage forms. Formulating ayurvedic powders into oro-dispersible tablets can be one of the alternatives to overcome problems related to use of ayurvedic powder formulations. Considering this, the present study was designed to formulate oro-dispersible tablets of model ayurvedic powders Talisadi^12,13 and Sitopaladi^14,15 using common excipients and evaluate them for effect of formulation on pharmacological and therapeutic activity of ayurvedic formulations.

2. MATERIALS AND METHODS:

Talisadi and Sitopaladi powder were purchased from Wonder Herbals Ltd Hyderabad India. All the other excipients were procured from S. D. Fine Chemicals Mumbai India. All reagents were of AR grade and used as received.

2.1. Preparation of oro-dispersible tablets:

All ingredients were mixed and the blend was air-dried and compressed using CADMACH 8 punch rotary tablet machine at a fixed compression force. The mean weight and diameter of the tablets were 650 mg and 9 mm, respectively. Amongst prepared formulations best formulations were only used for in vivo evaluation in rats. Formula for oro-dispersible tablets of talisadi and Sitopaladi powder (optimized batch) is given in Table 1.

Table1: Formulation of Oro-dispersible Tablets

Ingredients (mg)

Talisadi

Sitopaladi

PVP

Mannitol

Lactose

Cros-povidone

stearate

Talc

Trisodium Citrate

Sodium Saccharine

500

2.2. Evaluation of Tablets:

In vitro evaluation: All the formulation batches of oro-dispersible tablets were evaluated for the following formulation related parameters as per standard procedure

Weight variation, Hardness, Friability, Disintegration time, and Palatability Test by panel method^16,17.

2.3. In vivo evaluation:

In vivo evaluation was carried out by evaluating cough bouts suppression by drug and standard. Cough was induced in rats by exposing them to SO2 gas^18,19,20 generated by reaction of water (H₂O) with sodium nitrite (Na₂SO₃).

2.3.1. Experimental animals:

Albino rats (200-280g) were used in the present research. They were procured from Sainath agencies, Musheerabad (282/99/CPCSEA). After randomization into various groups and before initiation of experiment, the rats were acclimatized for a period of 10 days. Animals were housed in polypropylene cages and maintained under standard environmental conditions such as temperature (26 ± 2ºc), relative humidity (45-55%) and 12hr dark/light cycle. The animals were fed with rodent pellet diet (Golden Mohur Lipton India Ltd.) and water ad libitum. The study protocol was approved from the institutional animal ethics committee (IAEC) before commencement of experiment IAEC (1292/ac/09/CPCSEA).

Table 2: Animal groups and their respective treatment

Group	I	II	III	IV	V	VI	VII
Average Weight	250 g	225 g	200 g	235 g	250 g	220 g	225 g
Drug Treatment	No Drug	1% Acacia solution	Codeine in 1% acacia suspension	Talisadi powder in 1% acacia suspension	Sitopaladi powder in 1% acacia suspension	Talisadi ODT in 1% acacia suspension	Sitopaladi ODT in 1% acacia suspension
Dose	--	--	10mg/kg	50mg/kg	50mg/kg	50mg/kg	50mg/kg

2.3.2. Evaluation of anti-tussive activity:

Sulphur dioxide (SO₂) induced cough method of Miyagoshi et al.¹⁶ for evaluation of antitussive activity modified and simplified by us was used. The earlier researchers have used sodium hydrogen sulfite (NaHSO3) and sulphuric acid (H₂SO₄) for generating SO₂ gas. In this experiment instead of NaHSO3, Na₂SO₃was used and reacted with water to generateSO2_.The reaction involved is as follows:

Na₂SO₃ + H₂O = SO₂+ NaOH

First a desiccator fitted with removable mesh at the bottom was taken. Beneath the mesh, Na₂SO₃ was placed in a small petri dish. Small amount of distilled water was added in petri dish containing Na₂SO₃ using the pipette and the desiccator was closed carefully. This results in generation and accumulation of SO₂ in the desiccator chamber. After 20 seconds, rats were placed one by one on the mesh and allowed to inhale the SO₂ vapors which initiates cough. After 45 sec of SO₂ exposure, the rat was removed and kept in observation chamber for counting the cough bouts for a period of five minutes.

2.3.3. Cough bouts scoring:

To avoid the observer bias, cough bouts were independently counted each time by two observers using digital counters and stopwatches. If for any reading the difference in cough bout count among two observers was more than 10%, the experiment was discarded. Final readings are mean of these two observations.

2.3.4. Drug treatment:

All drugs were administered orally (p.o.). Albino rats were divided into seven groups of six animals each. Group I served as normal control and was not administered any drug. Group II was given 1% acacia solution in distilled water (vehicle) , group III received standard drug i.e. codeine 10 mg/kg, p.o. Group IV and V were given ayurvedic powder Talisadi and Sitopaladi at a dose of 50 mg/kg, group VI and VII were given ODT of talisadi and Sitopaladi respectively at a dose of 50 mg/kg. Control rats are exposed to sulphur dioxide individually for 45 seconds and number of cough bouts exhibited are recorded for 5 minutes. Repeat the same procedure with standard codeine treated rats, ayurvedic powder treated rats and ayurvedic ODT treated rats one hour after respective treatment and the cough bouts are recorded. The detailed information of animal groups is given in Table 2.

3. RESULT AND DISCUSSION:

3.1. Evaluation of tablets:

The formulations were found to be having very good quality attributes. All the formulations were compling with pharmacopeial standards in evaluated parameters with disintegration time, most crucial parameter in case of oro-dispersible tablets in both the selected formulations being less than one minutes (data not shown).

The panel method of taste evaluation also indicated that more than 80% volunteers were satisfied with the taste of tablets and consider non bitter and acceptable as compared to plain powder for which all the volunteers reported its taste to be bitter and unacceptable (data not shown).

Table No. 3: Cough suppressing activity in different Animal groups

Group		I	II	III	IV	V	VI	VII
Cough Bouts	Before Treatment	59±3.9	58±1.2	58±3.4	61±4.0	59±3.6	60±2.7	56±3.5
Cough Bouts	After Treatment	--	55±3.6	20±2.8	33±2.9	28±3.7	36±2.1	29 ±1.3
Reduction in cough Bouts			3	38	28	31	24	33

3.2. In vivo evaluation:

To evaluate the invivo antitussive potential of ayurvedic powder formulation and its invivo comparative assessment with formulated oro-dispersible ayurvedic tablets by using so₂induced cough model in albino rats. The present invivo research was carried with a rationale to assess effect of addition of excipients in the formulation of oro-dispersible tablets on the effectiveness of ayurvedic powder. The results are summarised in table 3.

The SO₂ gas generated was effective in inducing cough bouts and causing cough. From the results it can be seen that the ayurvedic powders and ODT have very good anti-tussive and cough suppressing activity. Though the anti-tussive effects of ODT and ayurvedic powders was found to be somewhat less than standard drug Codeine (cough bouts =20±2.8), till it was comparable. Ayurvedic powders (IV= Talisadi & V= sitophaladi) treated rats caused a marked reduction in cough bouts after treatment.(i.e IV, from 61±4.0 to 33±2.9 & V, 59±3.6 to 28±3.7.) when compared to control rats. (II, from 58±1.2 to 55±3.6). It was observed that sitopaldi powder has relatively superior cough suppressing activity as compared to talisadi. In case of ODT, Sitophaladi treated rats (VII, 56±3.5 to 29±1.3) have exhibited more significant reduction in cough bouts than Sitopaladi powder. Talisadi ODT (VI, 60±2.7 to 36±2.1) was having slightly less activity than talisadi powder. The inherent comparatively low activity of ayurvedic drug may be the reason in case of talisadi. Sitopaladi activity may be enhanced due to addition of excipients because of enhanced demulcent potential of Sitopaladi.

Thus the negligible changes in activity and substantial improvement in accuracy and ease of administration and increased patient compliance as indicated by palatability taste.

4. CONCLUSION:

The in-vivo study confirms that ayurvedic powders sitopaldi and talisadi have very good cough suppressing and anti-tussive activity. There is no or insignificant effect on effectiveness of ayurvedic powders after formulating into modern formulation like Oro-dispersible tablet. Moreover it may lead to enhanced activity like in case of Sitopaladi. Thus it can be concluded that formulation of oro-dispersible tablets is a practical approach to improve ease and accuracy of administration as well as enhance patient compliance without affecting effectiveness of ayurvedic powders.

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Received on 23.05.2016 Modified on 10.06.2016

Res. J. Pharm. Dosage Form. & Tech. 2016; 8(3): 177-180.

DOI: 10.5958/0975-4377.2016.00024.0