Naresh Hiraram Choudhary et al. / Journal of Pharmacy Research 2012,5(7),3791-3799 Review Article Available online through ISSN: 0974-6943 http://jprsolutions.info Orally Disintegrating Drug Delivery Systems Naresh Hiraram Choudhary*, Manoj Shivaji Kumbhar, Deepak Annasaheb Dighe, Anita Prakash Sapkale, Meera Chandradatt Singh Department of Pharmaceutics, Sinhgad Technical Education Society’s, Smt. Kashibai Navale College of Pharmacy, Kondhwa [Bk], Pune, Maharashtra, India. Received on:07-04-2012; Revised on: 12-05-2012; Accepted on:16-06-2012 ABSTRACT Many patients have difficulty in swallowing tablets and hard gelatin capsules and consequently do not take medicine as prescribed. It is estimated that 50% of the population is affected by this problem, which results in a high incidence of noncompliance and ineffective therapy. The difficulty is experienced in particular by pediatric and geriatric patients, but it also applies to people who are ill in bed and to those active working patients who are busy or travelling, especially those who have no access to water. Such problems can be resolved by means of Orally Disintegrating Tablets (ODTs) which does not require water to aid swallowing. ODTs are placed on the tongue, allowed to disperse or dissolve in the saliva, and then swallowed without the need of water. Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the stomach. In these cases, the bioavailability of drug is significantly greater than those observed from standard dosage forms. ODTs can be formulated using different techniques like freeze drying, cotton candy process, moulding, sublimation, and direct compression. The various patented technology includes Zydis®, QuickSolv®, Lyoc®, Flashdose®, OraSolve®, Ziplet technology, Frosta®, DuraSolve®, and Wowtab®. ODTs offer many advantages like improved patient compliance, rapid onset of action, improved bioavailability. The future of ODTs lies in the development of ODTs with controlled release properties. Key words: Orally Disintegrating Tablets (ODTs), Zydis®, Cotton candy process, Moulding, Direct compression, Superdisintegrants. INTRODUCTION Many patients have difficulty swallowing tablets and hard gelatin capsules Despite a surge of orally disintegrating tablets in the market in the recent and consequently do not take medications as prescribed. It is estimated that years, they potentially can be confused with other solid oral dosage forms 50% of the population is affected by this problem, which results in a high that are consumed without additional water intake, including lozenges, buccal incidence of noncompliance and ineffective therapy. The demand for solid tablets, chewable tablets and effervescent tablets. Lozenges and buccal tab- dosage forms that can be dissolved and suspended in water, chewed, or lets are intended to dissolve slowly in the mouth, whereas, ODTs must rapidly dissolved in the mouth is particularly strong in the pediatric and disperse or dissolve in the mouth quickly, within seconds. Chewable tablets geriatric markets, with further application to other patients who prefer the are also different from orally disintegrating tablets because they require manual convenience of a readily administered dosage form. Because of the increase in chewing action by the patient before they can be swallowed. The disintegra- the average human life span and the decline, with age, in swallowing ability, tion times are longer for the chewable tablets as compared to the ODTs. oral tablet administration to patients is a significant problem and has become Effervescent tablets require preparatory steps before administration of the the object of public attention [1]. The problem can be resolved by the creation drug [5, 6]. of Orally Disintegrating Tablets (ODTs). ODTs rapidly disintegrate in the mouth without chewing upon oral administration and without the need for One of the greatest benefits of ODTs over conventional tablets is enhanced water, unlike other drug delivery systems and conventional oral solid imme- patient compliance and acceptance related to both feasibility and conve- diate-release dosage form [2]. ODTs dosage forms, also commonly known as nience of dosage administration [7]. Population having difficulty in swallow- fast melt, quick melts, fast disintegrating, or dispersible systems have the ing intact tablets and hard gelatin capsules include pediatric and geriatric, unique property of disintegrating the tablet in the mouth in seconds [3]. patients who are bedridden, mentally retarded, uncooperative, nauseous, and those suffering from nervous or anatomical disorder of the larynx or esopha- The dosage forms are placed in the mouth, allowed to disperse or dissolve in gus, or on reduced liquid intake diets also cannot swallow conventional tab- the saliva, and then are swallowed in the normal way. Less frequently, they lets. In such patients practitioners would expect much better compliance and are designed to be absorbed through the buccal and esophageal mucosa as the therapeutics outcomes by administering ODTs instead of conventional tab- saliva passes into the stomach. In the latter case, the bioavailability of a drug lets [8]. Patient compliance can be enhanced by designing orally disintegrating from fast dispersing formulations may be even greater than that observed for tablets that have pleasant taste and texture because many people simply do standard dosage forms. Furthermore, side effects may be reduced if they are not enjoy swallowing solid tablets. People who take medicine such as-needed caused by first pass metabolites [1, 4]. Orally disintegrating dosage forms are basis and active people who do not have convenient access to water could often formulated for existing drugs with an intention to extend the patent life easily take them as well [6]. Other advantages includes benefit of liquid medi- of the drug through product differentiation. They are evaluated against the cation in the form of solid preparation, more rapid drug absorption from the innovator drug in a bioequivalence study in humans to establish comparabil- pre-gastric area i.e. mouth, pharynx and esophagus which may produce rapid ity of pharmacokinetic parameters. onset of action, pregastric absorption can result in improved bioavailability, reduced dose and improved clinical performance by reducing side effect, new *Corresponding author. business opportunities like product differentiation, line extension and life- Naresh Hiraram Choudhary. cycle management, exclusivity of product promotion and patent-life exten- Department of Pharmaceutics, Sinhgad sion [9,10,11]. Technical Education Society’s, Smt. Kashibai Navale College of Pharmacy, Kondhwa [Bk], Orally disintegrating tablet drug delivery does, however, have certain limita- Pune, Maharashtra, India. tions. Because ODTs require the users to produce their own saliva, those Journal of Pharmacy Research Vol.5 Issue 7.July 2012 3791-3799 Naresh Hiraram Choudhary et al. / Journal of Pharmacy Research 2012,5(7),3791-3799 with very dry mouth may not benefit. Production of saliva depends not only Freeze-Drying or Lyophilization on the drug product formulation but the ability and condition of the user. This technique forms the basis of Zydis (Cardinal Health), Quicksolv (Janssen Also, the administration of ODTs to increase compliance in uncooperative Pharmaceutica), Lyoc (Pharmalyoc), and NanoCrystal™ (Elan) technologies patients, such as those being treated for mental illness, does not guarantee which are used to manufacture ODTs [17]. Zydis Technology utilizes a unique compliance. Patients have found various ways of hiding the medication such freeze-drying process to manufacture finished dosage units which signifi- as sticking the Zydis tablets behind the teeth to avoid swallowing the medi- cantly differ from conventional oral systems. The process involves the fol- cation [12]. Nonetheless, ODTs offer practitioners an added tool in enhancing lowing steps: compliance in some patient population [13]. RECENT FDA GUIDANCE ON ODT TECHNOLOGIES Stage 1 - Bulk preparation of an aqueous drug solution or suspension and its The emergence of multiple ODT technology platforms created some regula- subsequent precise dosing into pre-formed blisters. It is the blister that tory challenges due to increasing variance in the critical product attributes of actually forms the tablet shape and is, therefore, an integral component of the ODTs, notably disintegration time and tablet size. Hypothetically, in an total product package. abbreviated new drug application, the disintegration time of a generic prod- Stage 2 - Passing the filled blisters through a specially designed cryogenic uct could be 30–45 s, and the disintegration time of a reference product 0–10 freezing process to control the ultimate size of the ice crystals which ensures s. Prolonged disintegration times may result in failure to meet the defining that the tablets possess a porous matrix to facilitate the rapid disintegration performance characteristics of the ODTs dosage form, such that the product property. These frozen units are then transferred to large-scale freeze dryers might require water for administration or chewing to facilitate swallowing. for the sublimation process, where the majority of the remaining moisture is Where the patient or caregiver’s expectation is for rapid dispersion in the removed from the tablets. mouth, larger units with slower disintegration times could result in confusion Stage 3 -Sealing the open blisters using a heat-seal