Formulation and Evaluation of Effervescent Floating Tablets of Domperidone

 

Dr Y. Krishna Reddy¹*, K. Satheesh Kumar²

^1,2Department of Pharmaceutics, Nalanda College of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad, Telangana.

 

ABSTRACT:

The present study was undertaken to prolong the release of orally administered drug. The objective of the study was to formulate the sustained release floating tablet of Domperidone. The floating tablets of Domperidone were prepared by direct compression method. For this, polymers like HPMC K4M, Sodium CMC and Carbopol p934 were used in various concentrations. Sodium bicarbonate was used as a floating effervescent agent. The formulations were evaluated for various physical parameters, floating lag time, In-vitro drug release. From the results obtained, Formulation F9 gives desirable Sustained effect for 12 hours having 98.42% drug release at the end of the 12 hours. formulation F9 contain Carbopol p934 in concentration 2mg.

 

 

 

INTRODUCTION:

Oral delivery of drugs is the most preferable route of drug delivery. Oral route is considered most natural, uncomplicated, convenient and safe due to its ease of administration, patient compliance and flexibility in formulation and cost effective manufacturing process ¹.  Many of the drug delivery systems, available in the market are oral drug delivery type systems Pharmaceutical products designed for oral delivery are mainly immediate release type or conventional drug delivery systems, which are designed for immediate release of drug for rapid absorption.

 

These immediate release dosage forms have some limitations such as:

1.     Drugs with short half-life require frequent administration, which increases chances of missing dose of drug leading to poor patient compliance.

2.     A typical peak-valley plasma concentration-time profile is obtained which makes attainment of steady state condition difficult.

3.     The unavoidable fluctuations in the drug concentration may lead to under medication or overmedication as the C_ss values fall or rise beyond the therapeutic range.

4.     The fluctuating drug levels may lead to precipitation of adverse effects especially of a drug with small therapeutic index, whenever overmedication occurs.² In order to overcome the drawbacks of conventional drug delivery systems, several technical advancements have led to the development of controlled drug delivery system that could revolutionize method of medication and provide a number of therapeutic benefits.³

 

Controlled Drug Delivery Systems:

Controlled drug delivery systems have been developed which are capable of controlling the rate of drug delivery, sustaining the duration of therapeutic activity and/or targeting the delivery of drug to a tissue.⁴

Controlled drug delivery or modified drug delivery systems are divided into four categories.

1    Delayed release

2    Sustained release

3    Site-specific targeting

4    Receptor targeting

 

More precisely, controlled delivery can be defined as:

1.     Sustained drug action at a predetermined rate by maintaining a relatively constant, effective drug level in the body with concomitant minimization of undesirable side effects.

2.     Localized drug action by spatial placement of a controlled release system adjacent to or in the diseased tissue.

3.     Targeted drug action by using carriers or chemical derivatives to deliver drug to a particular target cell type.

4.     Provide physiologically/therapeutically based drug release system. In other words, the amount and the rate of drug release are determined by the physiological/therapeutic needs of the body.⁵

 

AIM AND OBJECTIVE:

Aim:

The aim of the present work is to formulate and evaluate gastro retentive floating tablets of Domperidone using Various polymers.

 

Objectives:

The Gastro Retentive drug delivery systems can be retained in the stomach and assist in improving the oral sustained delivery of drugs that have an absorption window in a particular region of gastrointestinal tract. These systems help in continuously releasing the drug before it reaches the absorption window, thus ensuring optimal bioavailability.

 

Domperidone is a peripherally selective dopamine D2 receptor antagonist and is used as an antiemetic, gastroprokinetic agent, and galactagogue.

 

In the present investigation floating tablets of Domperidone were prepared by direct compression using Various polymers.

 

MATERIALS AND METHOD MATERIALS: Domperidone was Provided by SURA LABS, Dilsukhnagar, Hyderabad.  HPMC K4M, Sodium CMC, Carbopol p934 was gift sample from SURA LABS, Dilsukhnagar, Hyderabad, India Lactose was purchased from IndchemInternational Ltd, Mumbai, India, NaHCO3 was purchased from S.D. Fine Chemicals, Mumbai, India, Magnesium striate was purchased from Loba chemicals, Mumbai, India and Talc was purchased from Apex Chemicals, Ahmedabad, India.

 

METHODOLOGY:

FORMULATION OF TABLETS:

Table no 1: Formulation composition for Floating tablets:

 

RESULTS AND DISCUSSION:

Analytical Method:

Determination of absorption maxima:

The standard curve is based on the spectrophotometry. The maximum absorption was observed at 284 nm.

 

Calibration curve:

Graphs of Domperidone was taken in 0.1N HCL (pH 1.2)

 

Table no 2: Observations for graph of Domperidone in 0.1N HCl

Conc [µg/mL]	Abs
0	0
5	0.131
10	0.224
15	0.339
20	0.446
25	0.543

 

 

Standard graph of Domperidone was plotted as per the procedure in experimental method and its linearity is shown in Table 8.1 and Fig 8.1. The standard graph of Domperidone showed good linearity with R² of 0.998, which indicates that it obeys “Beer- Lamberts” law.

 

Fig no 1: Standard graph of Domperidone in 0.1N HCL

 

Preformulation parameters of powder blend:

Table no 3: Pre-formulation parameters of blend

 

Tablet powder blend was subjected to various pre-formulation parameters. The angle of repose values indicates that the powder blend has good flow properties. The bulk density of all the formulations was found to be in the range of 0.418±0.054 to 0.585±0.065 (gm/ml) showing that the powder has good flow properties. The tapped density of all the formulations was found to be in the range of 0.489±0.015 to 0.678±0.041 showing the powder has good flow properties. The compressibility index of all the formulations was found to be below 15.96 which shows that the powder has good flow properties. All the formulations has shown the hausners ratio ranging between 1.2 to 1.19 indicating the powder has good flow properties.

 

Optimization of sodium bicarbonate concentration:

Three formulations were prepared with varying concentrations of sodium bicarbonate by direct compression method and three more formulations were prepared by wet granulation method to compare the floating buoyancy in between direct and wet granulation methods. The formulation containing sodium bicarbonate in 10mg concentration showed less floating lag time in wet granulation method and the tablet was in floating condition for more than 12 hours.

 

Quality Control Parameters For tablets:

Tablet quality control tests such as weight variation, hardness, and friability, thickness, Drug content and drug release studies were performed for floating tablets.

Table no 4: In vitro quality control parameters

All the parameters such as weight variation, friability, hardness, thickness, drug content were found to be withinlimits.

 

In Vitro Drug Release Studies

Table no 5: Dissolution data of Floating Tablets

 

 

Fig No 2:  Dissolution data of Domperidone Floating tablets containing All formulations (HPMC K4M, Sodium CMC, Carbopol 934)

 

 

From the dissolution data it was evident that the formulations prepared with HPMC K4M as polymer were retarded the drug release more than 12 hours.

 

Whereas the formulations prepared with Sodium CMC retarded the drug release up to 12 hours in the concentration 2 mg. In higher concentrations the polymer was unable to retard the drug release.

 

Whereas the formulations prepared with Carbopol 934 retarded the drug release up to 12 hours in the concentration 2 mg. In higher concentrations the polymer was unable to retard the drug release.

 

Hence from the above dissolution data it was concluded that F9 formulation was considered as optimised formulation because good drug release (98.42%) in 12 hours.

 

Drug – Excipient compatability studies:

Fourier Transform-Infrared Spectroscopy:

 

Fig no 3: FTIR Spectrum of pure drug

 

Fig No 4: FTIR Spectrum of optimised formulation

 

There was no disappearance of any characteristics peak in the FTIR spectrum of drug and the polymers used. This shows that there is no chemical interaction between the drug and the polymers used. The presence of peaks at the expected range confirms that the materials taken for the study are genuine and there were no possible interactions.  

Domperidone are also present in the physical mixture, which indicates that there is no interaction between drug and the polymers, which confirms the stability of the drug.   

 

CONCLUSION:

The floating tablets of Domperidone were formulated by direct compression polymer like HPMC K4M, Sodium CMC and Carbopol p934 used for sustained release. The formulations were evaluated for various parameters like Hardness, Friability, Weight variation, Floating lag time, Floating time, % Drug Content, In-vitro drug release. From the results obtained, it was concluded that Formulation F9 containing Carbopol p934 shows a desirable Sustained effect for 12 hours having 98.42% release at the end of the 12 hours.

 

АCKNOWLEDGEMENT:

Thе Authors arе thankful to Sura Labs, Dilshukhnagar, Hydеrabad for providing thе nеcеssary facilitiеs for thе rеsеarch work.

 

REFERENCES:

1.      Leon Lachman, Herbert A. Liberman, The Theory and Practice of Industrial Pharmacy: p.293-302.

2.      Robinson JR, lee V.H.L, Controlled Drug Delivery: Fundamentals and Applications, 2nd edn. Marcel Dekker, New York: (1978) p.24-36.

3.      Brahmankar D.M, Jaiswal S.B, Biopharmaceutics and Pharmacokinetics a Treatise, 1st ed. Vallabh Prakashan; New Delhi: (1995) p.64-70.

4.      Chein Y.W, Novel Drug Delivery Systems, 2nd Ed.: Marcel Dekker; New York: (1992) p.4-56.

5.      Ansel, Pharmaceutical Dosage Form and Drug Delivery System, Lipincott, 7th Edition: p. 553.

 

 

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