Formulation and Evaluation of Meclizine Hcl Orally Dispersible Tablets by using Natural Super Disintegrants

The present study is on Meclizine HCL orally disintegrating tablets. meclizine HCL is used for the treatment of many different types of bacterial infections such as bronchitis, sinusitis, tonsillitis, ear infections, skin infections, gonorrhea, and urinary tract infections. meclizine HCL is a β-lactam type antibiotic. More specifically, it is a second-generation cephalosporin. Natural super disintegrates like xanthum gum and algenic acid are added to the formula to increase its disintegration, Orodispersible tablets of Meclizine Hcl were formulated by the Natural Superdisintegrant addition method by direct compression technique. All the formulations were evaluated for disintegration time, hardness and friability, this Superdisintegrant addition method exhibits the lowest disintegration time 29 sec, hence it is ranked as the best among the methods. All the formulations were evaluated for weight variation 226.3, hardness 5.1 , friability0.29, drug content uniformity 99.5, wetting time 28 sec for in-vitro dissolution study. Among all the formulations containing naturally super disintegrates like algenic acid and xanthumgum was considered to be the best formulation, which release up to 99.6% of the drug in 20 mints. 53 Introduction Drug delivery systems (DDS) are a strategic tool for expanding markets/indications, extending product life cycles and generating opportunities. The DDS makes a significant contribution to global pharmaceutical sales through market segmentation, and are moving rapidly. Drug delivery systems are becoming increasingly sophisticated as pharmaceutical scientists acquire a better understanding of the physicochemical and biochemical parameters pertinent to their performance. 1 Oral drug delivery has been known for decades as the most widely utilized routes of the administered among all the routes that have been employed for the systemic delivery of drug via various pharmaceutical products of different dosage forms. The reasons that the oral route achieved such popularity may be in part attributed to its ease of administration1. It has been reported that Dysphagia (difficulty in swallowing) is common among all age groups and more specific with pediatric, geriatric population along with institutionalized patients and patients with nausea, vomiting, and motion sickness complications. ODTs with good taste and increase the flavor acceptability of bitter drugs by various groups of population. Orally disintegrating tablets are also called as orodispersible tablets, quick disintegrating tablets, mouth dissolving tablets, fast disintegrating tablets, fast dissolving tablets, rapid dissolving tablets, porous tablets, and rapimelts. However, of all the above terms, United States pharmacopoeia (USP) approved these dosage forms as ODTs. Recently, European Pharmacopoeia has used the term orodispersible tablet for tablets that disperses readily and within 3 min in mouth before swallowing. Despite of tremendous advancements in drug delivery, the oral route remains the perfect route for the administration of therapeutic agents because the low cost of therapy, ease of administration lead to high levels of patient compliance. M. Vinod Kumar, IJPSR 2016, 2:1 International Journal of Pharma Sciences and Scientific Research Volume 2 Issue 1, April 2016 2 54 It is always the aim of a scientist or a dosage form designed to enhance the safety of a drug molecule while maintaining its therapeutic efficacy. Recent advances in NDDS aim for the same by formulating a dosage form, convenient to be administered so as to achieve better patient compliance. Mouth Dissolving Tablet (MDT) is one among such approaches. Improved patient compliance has achieved enormous demand. Consequently the demand for their technologies is also increasing many folds. To develop a chemical entity, a lot of money, hard work and time are required. So the focus is rather being laid on the development of new drug delivery systems for already existing drugs, with enhanced efficacy and bioavailability, thus reducing the dose and dosing frequency to minimize the side effects. The oral route of administration is the most preferred route due to its many advantages like ease of administration, accurate dosage, self-medication, pain avoidance, versatility and patient compliance. Tablets and capsules are the most popular dosage forms.2,3 But one important drawback of such dosage forms is dysplasia or difficulty in swallowing. This is seen to afflict nearly 35% of the general population. This disorder is also associated with a number of pathological conditions, including stroke, Parkinson’s disease, neurological disorders, AIDS etc. 2,3 • Parkinsonism • Motion sickness • Unconsciousness • Elderly patients • Children • Mentally disabled persons M. Vinod Kumar, IJPSR 2016, 2:1 M. Vinod Kumar, IJPSR 2016, 2:1 International Journal of Pharma Sciences and Scientific Research Volume 2 Issue 1, April 2016 3 55 • Ideal Properties of ODTs: 4,5,6 The performance of ODTs depends on the technology used during their manufacture. The necessary property of such tablets is the ability to disintegrate rapidly and disperse or dissolve in saliva, thereby obviating the need for water. Various technologies have been developed that enable ODT to perform this unique function. An ideal ODT should meet the following criteria: • Does not require water for oral administration yet disintegrates and dissolves in oral cavity within a few seconds • Has sufficient strength to withstand the rigors of the manufacturing process and post-manufacturing handling • Allow high drug loading • Has a pleasant mouth feel • Is insensitive to environmental conditions such as humidity and temperature is adaptable and amenable to existing processes and packaging machineries. 1.2 Advantages of Orodispersible tablet:4,5,6 1. No need of water to swallow the tablet. • Can be easily administered to pediatric, elderly and mentally disabled patients. • Accurate dosing as compared to liquids. • Dissolution and absorption of drug are fast, offering a rapid onset of action. • Bioavailability of drugs is increased as some drugs are absorbed from mouth, pharynx and esophagus through saliva, passing down into the stomach. • Advantageous over liquid medication in terms of administration as well as transportation. • First pass metabolism is reduced, thus offering improved bioavailability and thus reduced dose and side effects. • Free of the risk of suffocation due to physical obstruction when swallowed, thus offering improved safety. • Suitable for sustained/controlled release actives. • Unavailability of water To solve the above-mentioned problems, pharmaceutical technologists have put in their best efforts to develop a Fast dissolving drug delivery, i.e. Oro dispersible tablet that disintegrates and dissolves rapidly in the patient’s mouth, within a 15 Sec-3 min without the need for drinking water or chewing. Most of the ODTs include certain super disintegrates and taste masking agents. M. Vinod Kumar, IJPSR 2016, 2:1 International Journal of Pharma Sciences and Scientific Research Volume 2 Issue 1, April 2016 4 56 Figure 1: Figures showing Advantages of Orodispersible tablet 1.2. The need for development of ODT: 7,8,9 The need for non-invasive delivery systems persists due to patients’ poor acceptance of, and compliance with, existing delivery regimes, limited market size for drug companies and drug uses, coupled with the high cost of disease management. 1.2. 1. Patient Factors: Orally disintegrating dosage forms are particularly suitable for patients, who for one reason or the other; find it inconvenient to swallow traditional tablets and capsules with an 8-Oz glass of water. These include the following • Pediatric and geriatric patients who have difficulty in swallowing or chewing solid dosage forms • Patients who are unwilling to take solid preparation due to fear of choking • Very elderly patients who may not be able to swallow a daily dose of antidepressant. • An eighty year old with allergies who desires a more convenient dosage form than antihistamine syrup. • A middle-aged woman undergoing radiation therapy for breast cancer may be too nauseous to swallow her H2blocker. • A schizophrenic patient in an institutional setting who may try to hide a conventional tablet under his or her tongue to avoid their daily dose of a typical antipsychotic. • A patient with persistent nausea, who may be journeying, or has little or no access to water. 1.2. 2. Effectiveness Factor: Increased bioavailability and faster onset of action are a major claim of these formulations. Dispersion in saliva in oral cavity causes pregastric absorption from some formulations in those cases where drug dissolves quickly. Buccal, pharyngeal and gastric regions are all areas of absorption of many drugs. Any pregastric absorption avoids first pass metabolism and can be a great advantage in drugs that undergo a great deal of hepatic metabolism. Furthermore, safety profiles may be improved for drugs that produce significant amounts of toxic metabolites mediated by first-pass liver metabolism and gastric metabolism, and for drugs that have a substantial fraction of absorption in the oral cavity and pregastric segments of GIT. 1.2. 3. Manufacturing and Marketing Factors: Developing new drug delivery technologies and utilizing them in product development is critical for pharmaceutical industries to survive, regardless of their size. As a drug nears the end of its patent life, it is common for pharmaceutical manufacturers to develop a given drug entity in a new and improved dosage form. A new dosage form allows a manufacturer to extend market exclusivity, product line extension, and extend patent protection, while offering its patient population a more convenient dosage form. This leads to increased revenue, while also targeting underserved and under-treated patient populations. As examples, Eisai Inc. Launched Aricept ODT, a line extension of donepezil fo