Formulation and In-vitro Evaluation of Buccal Tablets of Hydralazine HCl

 

Dr Y. Krishna Reddy*, P. Shirisha

Department of Industrial Pharmacy, Nalanda College of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad, Telangana.

 

ABSTRACT:

Hydralazine HCL is a medication used to treat high blood pressure and heart failure. This includes high blood pressure in pregnancy and very high blood pressure resulting in symptoms. The mucoadhesive buccal tablets of Hydralazine HCL were papered by direct compression method using natural and synthetic polymer like Pectin, Sodium alginate and Carbopol. The compatibility studies of drug and excipient were performed by FT-IR spectroscopy. After examining the flow properties of the powder blends the results were found to be within prescribed limits and indicated good flowing property, hence it was subjected to compression. The tablets were evaluated for post-compression parameters like weight variation, hardness, thickness, friability, drug content uniformity, surface pH, in-vitro studies like Moisture absorption and drug release. Formulation (H2) containing Pectin showed exhibited optimum  drug  release  (99.32%). Surface pH was found to be range of salivary pH. All the evaluation parameters given the positive result and comply with the standards.

 

 

 

INTRODUCTION:

Buccal delivery of drugs provides an attractive alternative to the oral route of drug administration, particularly in overcoming deficiencies associated with the latter mode of dosing. Problems such as first pass metabolism and drug degradation in the GIT environment can be circumvented by administering the drug via buccal route. Moreover, the oral cavity is easily accessible for self-medication and be promptly terminated in case of toxicity by removing the dosage form from buccal cavity.

 

It is also possible to administer drugs to patients who cannot be dosed orally via this route Successful buccal drug delivery using buccal adhesive system requires at least three of the following (a) A bioadhesive to retain the system in the oral cavity and maximize the intimacy of contact with mucosa (b) A vehicle the release the drug at an appropriate rate under the conditions prevailing in the mouth and (c) Strategies for overcoming the low permeability of the oral mucosa. Buccal adhesive drug delivery stem promote the residence time and act as controlled release dosage forms.

 

The use of many hydrophilic macromolecular drugs as potential therapeutic agents is their in adequate and erratic oral absorption. However, therapeutic potential of these compounds lies in our ability to design and achieve effective and stable delivery systems. Based on our current understanding, it can be said that many drugs can not be delivered effectively through the conventional oral route.

 

 

The main reasons for the poor bio-availability of many drugs through conventional oral route are:

ü Pre-systemic clearance of drugs.

ü The sensitivity of drugs to the gastric acidic environment which leads to gastric irritation. Limitations associated with gastro intestinal tract like variable absorption characteristics.

 

Buccal mucosa composed of several layers of different cells. The Epithelium is similar to stratified squamous epithelia found in rest of the at least one of which is biological nature are held together by means of interfacial forces.¹

 

Buccal drug delivery is a type of bioadhesive drug delivery especially it is a mucoadhesive drug delivery system is adhered to buccal mucosa.

Ø The term bioadhesion is commonly defined as an adhesion between two materials where at least one of the materials is of biological origin. In the case of bioadhesive drug delivery systems, bioadhesion often refers to the adhesion between the excipients of the formulation (i.e. the inactive media) and the biological tissue.

Ø The term mucoadhesion can be considered to refer to a sub group of bioadhesion and, more specifically, to the case when the formulation interacts with the mucous layer that covers a mucosal tissue.

 

The mucosal layer lines a number of regions of the body including gastrointestinal tract, urogenital tract, airway, ear, nose and eye. Hence mucoadhesive drug delivery system includes the following.

1.     Buccal delivery system

2.     oral delivery system

3.     Ocular delivery system

4.     Vaginal delivery system

5.     Rectal delivery system

^6.       Nasal delivery system²

 

Overview of the Oral Mucosa Structure The oral mucosa is composed of an outermost layer of stratified squamous epithelium. Below this lies a basement membrane, a lamina propria followed by the submucosa as the innermost layer18, 19 can be seen in figure 1. The epithelium of the buccal mucosa is about 40- 50 cell layers thick, while that of the sublingual epithelium contains somewhat fewer. The epithelial cells increase in size and become flatter as they travel from the basal layers to the superficial layers. The turnover time for the buccal epithelium has been estimated at 5-6 days³, and this is probably representative of the oral mucosa as a whole. The oral mucosal thickness varies depending on the site: the buccal mucosa measures at 500-800 μm, while the mucosal thickness of the hard and soft palates, the floor of the mouth, the ventral tongue, and the gingivae measure at about 100-200 μm. The composition of the epithelium also varies depending on the site in the oral cavity. The mucosae of areas subject to mechanical stress (the gingivae and hard palate) are keratinized similar to the epidermis. The mucosae of the soft palate, the sublingual, and the buccal regions, however, are not keratinized⁴. The keratinized epithelia contain neutral lipids like ceramides and acylceramides which have been associated with the barrier function. These epithelia are relatively impermeable to water. In contrast, nonkeratinized epithelia, such as the floor of the mouth and the buccal epithelia, do not contain acylceramides and only have small amounts of ceramide ^5-7. They also contain small amounts of neutral but polar lipids, mainly cholesterol sulfate and glucosyl ceramides. These epithelia have been found to be considerably more permeable to water than keratinized epithelia.

 

PURPOSE OF STUDY:

Bioadhesive buccal delivery of drugs is one of alternative to the oral route of drug administration, particularly drugs that are having poor bioavailability and first pass effect. The bioavailability of such drugs may be significantly improved if delivered through the buccal route. Administering the drug via the buccal route can circumvent problems such as drug degradation in the harsh gastrointestinal environment, inconvenience of parenteral administration. Recently much attention has been focused on the design and evaluation of buccal drug delivery systems keeping in view their potential for future market.

 

In particular, the buccal route appears to offer a series of advantages, such as good accessibility, robustness of the epithelium, facile removal of the dosage form in case of need, relatively low enzymatic activity, and possibility of elimination of the administered dosage from the buccal area by natural clearance mechanisms, satisfactory patient acceptance and compliance.

 

RATIONALE OF DRUG SELECTION:

The above advantages makes buccal drug delivery is an alternative route of administration for the drugs, which are undergoes first pass effect. Hydralazine HCL was selected as the model drug for the investigation because it has got certain characteristics that a drug should possess to get absorbed through the buccal route viz., high solubility and low molecular weight. Moreover it undergoes first-pass metabolism in the liver which is the reason for its lower bioavailability, so its bioavailability may be improved when delivered through buccal route. This molecule is satisfying general considerations for buccal drug delivery. Hence it is selected as drug candidate for bioadhesive buccal drug delivery.

 

AIM:

The aim of present work is to formulate and evaluate bioadhesive buccal tablets of Hydralazine HCL drug to release the drug unidirectionally in the buccal cavity. 

OBJECTIVE:

The main objective of the present study is to avoid first pass metabolism, prolonging duration of action of drug and to enhance the bioavailability of drug by using bioadhesive polymers like Pectin, Sodium alginate and Carbopol and Microcrystalline cellulose as a diluent, Magnesium stearate as a lubricant to perform all possible evaluation parameters.

 

MATERIALS AND METHODS:

MATERIALS:

Hydralazine HCL procured from Procured From Lupin Research Park (Pune, India), Provided by SURA LABS, Dilsukhnagar, Hyderabad. Pectin purchased from Zydus  Cadila,  Ahmedabad. Sodium alginate purchased from Acurate Pharma. Carbopol, Talc Magnesium Stearate, purchased from Sd fine Chem.Ltd. Mumbai. Aspartame and  MCC purchased from Chemdie Corporation.

 

METHODOLOGY:

Preparation of Tablets:

Then the powder blend was compressed into tablets by the direct compression method using 7mm flat faced punches. The tablets were compressed using a sixteen station LAB PRESS rotary tablet-punching machine. The weight of the tablets were determined using a digital balance and thickness with digital screw gauge. Composition of the prepared bioadhesive buccal tablet formulations of Hydralazine HCL were given in Table 8.4.

 

Table1: Formulation Chart

 

RESULTS AND DISCUSSION:

Standard graph in phosphate buffer pH 6.8 (λ _max 230 nm)

Standard graph of Hydralazine HCL was plotted as per the procedure in experimental method and its linearity is shown in Table 9.2 and Fig 9.1. The standard graph of Hydralazine HCL showed good linearity with R² of 0.999, which indicates that it obeys “Beer- Lamberts” law.

 

Standard graph in phosphate buffer pH 7.4 (λ_max 230 nm)

Standard graph of Hydralazine HCL was plotted as per the procedure in experimental method and its linearity is shown in Table 9.3 and Fig 9.2. The standard graph of Hydralazine HCL showed good linearity with R² of 0.998, which indicates that it obeys “Beer- Lamberts” law.

 

Table2: Standard graph values of Hydralazine HCL in pH 6.8 phosphate buffer

 

 

Fig 1: Standard graph of Hydralazine HCL in pH 6.8 phosphate buffer

 

Table 3: Standard graph values of Hydralazine HCL in pH 7.4 phosphate buffer

 

 

Fig 2: Standard graph of Hydralazine HCL in pH 7.4 phosphate buffer

 

Evaluation:

Characterization of pre-compression blend:

The pre-compression blend of Hydralazine HCL buccal tablets were characterized with respect to angle of repose, bulk density, tapped density, carr’s index and hausner’s ratio. Angle of repose was less than 28.53º, carr’s index values were less than 14.28 for the pre-compression blend of all the batches indicating good to fair flowability and compressibility. Hausner’s ratio was less than 1.16 for all the batches indicating good flow properties.

Table4: Physical properties of pre-compression blend

 

Evaluation of buccal tablets:

Physical evaluation of Hydralazine HCL buccal tablets:

The results of the weight variation, hardness, thickness, friability and drug content of the tablets are given in Table 9.5. All the tablets of different batches complied with the official requirement of weight variation as their weight variation passes the limits. The hardness of the tablets ranged from 3.1 to 4.2 kg/cm² and the friability values were less than 0.75 % indicating that the buccal tablets were compact and hard. The thickness of the tablets ranged from 3.10 – 3.94 mm. All the formulations satisfied the content of the drug as they contained 96.78-99.56 % of Hydralazine HCL. Thus all the physical attributes of the prepared tablets were found to be practically within control limits.

 

Table5: Physical evaluation of Hydralazine HCL buccal tablets

 

In vitro release studies:

In vitro drug release studies were conducted in phosphate buffer pH 6.8 and the studies revealed that the release of Hydralazine HCL from different formulations varies with characteristics and composition of matrix forming polymers as shown in graphs 9.3 to 9.5.

 

 

Fig3:  In vitro dissolution data for formulations H1 – H9 by

 

From the above graphs it was evident that Pectin in the concentration of 24mg of polymer of the total tablet weight (H2) drug with other Two Formulations  H1, H3. Where as in H2 formulation the quantity of polymer was less hence it showed more drug retardation with more drug release that is 99.32 % in 8 hrs.

 

From the above graphs it was evident that Sodium alginate in the Polymer concentration of 12mg (H4), is showing better result 97.23% drug release when compared with other Two formulations H5, H6,  As the concentration of polymer increases the retarding of drug release decreased.

 

From the above graphs it was evident that Carbopol in the Polymer concentration 12mg formulation (H7), is showing better result 91.25 % drug release when compared with other two formulations. Where as in H8, H9 formulations the concentration become high and the drug release was less.

 

Table 6: In vitro dissolution data for formulations H1 – H9

FTIR

 

Fig 4: FTIR Peak of Pure drug Hydralazine HCL

Fig5: FTIR Peak of Optimised formulation

 

 

CONCLUSION:

The present research was carried out to develop mucoadhesive buccal tablets of Hydralazine HCL using natural and synthetic polymers like Pectin, Sodium alginate and Carbopol. The preparation process was simple, reliable and inexpensive. All the prepared tablet formulations were found to be good without capping and chipping. The mucoadhesive buccal tablets of Hydralazine HCL could be prepared using Pectin, Sodium alginate and Carbopol polymer by using direct compression method. The prepared mucoadhesive buccal tablets subjected to infrared spectrum study suggested that there was no drug -polymer interaction. All the prepared tablets were in acceptable range of weight variation, hardness, thickness, friability and drug content as per pharmacopeial specification. The surface pH of prepared buccal tablets was in the range of salivary pH, suggested that prepared tablets could be used without risk of mucosal irritation. The buccal tablets showed good Moisture absorption maintaining the integrity of formulation which is required for bioadhesion. The in-vitro release of Hydralazine HCL was extended for 8 h. Formulations H2 batch shows good in- vitro drug release 99.32%.

АCKNOWLEDGEMENT:

The Authors arе thankful to Sura Labs, Dilshukhnagar, Hydеrabad for providing thе necessary facilities for the research work.

 

REFERENCES:

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5.     Squier, C.A., Cox, P., and Wertz, P.W., Lipid content and water permeability of skin and oral mucosa, The J. Invest. Dermat, 96, 1991, 123-126.

6.     Squier, C.A. and Wertz, P.W. Structure and function of the oral mucosa and implications for drug delivery, in eds. M.J. Rathbone, Oral Mucosal Drug Delivery, Marcel Dekker, Inc., New York, New York, 1996, 1-26.

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Received on 17.02.2020          Modified on 08.03.2020

Accepted on 27.03.2020     ©AandV Publications All right reserved