The active moiety in pharmaceutical product cannot be therapeutically beneficial unless it has preference and acceptance by the patient. Thus, pleasant taste is important for the therapeutic success of the drug formulation.
Human tongue with taste receptors.
Sample Electronic tongue
Objectives of electronic tongue:
Identification between bitter, sweet and sour substances by using electronic tongue.
Separating the different substances eliciting the same taste (sour, bitter, sweet).
Identify drug preparations containing active substance and placebo substance.
Quantification of the effect of taste masking of bitter substances by sweet ones.
In order to allow ODTs to disintegrate in the oral cavity, they are made of
either very porous and soft-molded matrices or compressed into tablets with
very low compression force, which makes the tablets friable and/or brittle,
difficult to handle, and often requiring specialized peel-off blister packing that
may add to the cost.
AMOUNT OF DRUG
Application of technologies used for ODTs is limited by the amount of
drug that can be incorporated into each unit dose.
In case of Lyophilized dosage forms, drug dose must be
less than 400mg – insoluble drugs
less than 60mg -- soluble drugs
This parameter is particularly challenging when formulating a fast-dissolving oral films.
SIZE OF TABLET
The degree of ease when taking a tablet depends on its size. It has been
reported that the easiest size of tablet to swallow is 7-8 mm. While the
easiest size to handle was one larger than 8 mm.
Therefore, the tablet size that is both easy to take and easy to handle is
difficult to achieve
Several orally disintegrating dosage forms are hygroscopic and cannot
maintain physical integrity under normal conditions of temperature and
humidity. Hence, they need protection from humidity which calls for
specialized product packaging.
Water soluble drugs pose various formulation challenges because they form
eutectic mixtures, which result in freezing point depression and the
formation of a glassy solid that may collapse upon drying because loss of
supporting structure during the sublimation process.
This collapse can be prevented by using various matrix-forming excipients
like Mannitol which induces crystallinity and hence impart rigidity to the
ODTs being immediately releasing dosage forms and the absorption of
maximum amount of dose takes place in the pre-gastric region, these have
sort half life.
This character may render drug unsuitable for delivery as prolonged release
or sustained release dosage form.
COST OF THE TABLET
As ODTs are easily fragile, these products require special unit-dose
packaging which may add to the cost of the dosage form.
THE IDEAL CHARACTERISTICS OF DRUG
For disintegration and dissolution in oral cavity i.e., the pre-gastric absorption from an ODT include,
No bitter taste
Dose lower than 20mg
Small to moderate molecular weight
Good solubility in water and saliva
Partially nonionized at the oral cavity’s pH.
Ability to diffuse and partition into the epithelium of upper GIT.
Ability to permeate oral mucosal tissue.
Eg: More potent drugs like codeine are required in very low amount which
require diluent such as lactose to makeup volume of drug.
A sugar based matrix, called ‘Floss’ is used, which is made up of a
combination of excipients (crystalline sugars) alone or in combination with
Eg: Nurofen meltlet, a new form of Ibuprofen, as a mouth-dissolving tablet is the first commercial product prepared by this technology and launched by Biovail Corporation.
FLASH TAB TECHNOLOGY
Prographarm labs have a patent over this technology.
In this technology, microgranules of the taste-masked active drug are used.
Micro granules may be prepared by using conventional techniques like coacervation, micro encapsulation, and extrusion-spheronisation. All these processes utilize conventional tabletting technology.
These taste-masked micro crystals of active drug, disintegrating agent, a swelling agent and other excipients like soluble diluents etc are compressed to form a multiparticulate tablet that disintegrates rapidly.
Eg: Excedrin Quick Tabs (acetaminophen, caffeine) – head ache
DRUGS INCORPORATED IN ODTs
Analgesics and Anti-inflammatory Agents
Anti- muscarinic Agents
Anti- neoplastic Agents and Immunosuppressant's
Anti- protazoal Agents
Cardiac Inotropic Agents
Anti- parkinsonian Agents
Histamine H,-Receptor Antagonists etc…
Compatability studies = FTIR / DSC
Angle of repose Ө = tan -1 (h/r)
Determination of Bulk density = W / V o
Tapped density = W / V f
Hauser’s Ratio= Tapped density/Bulk density
compressibility index : CI = 100 (V o – V f )/ Vo
Some of the Marketed ODTs in India Famotidine (20-40 mg) Pepcid RPD Micronized Loratadine Claritin Reditab Nimesulide Nimulid -MD Olanzapine (5, 10, 15 or 20 mg) Zyprexa Zydis Piroxicam(10-20 mg) Feldene Melt Active Ingredient Name of product
WEIGHT VARATION TEST
I.P. procedure for uniformity of weight was followed, twenty tablets were taken and their weight was determined individually and collectively on a digital weighing balance. The average weight of one tablet was determined from the collective weight.
The weight variation test would be a satisfactory method of determining the drug content uniformity
The pharmacopoeial limit of friability test for a tablet is not more than 1% using Tablet friability apparatus, carried out at 25 rpm for 4 min (100 rotations).
This test is again not applicable for lyophilized and flash dose tablets, but is always recommended for tablets prepared by direct compression and moulding techniques to ensure that they have enough mechanical strength to withstand the abrasion during shipping and shelf life.
Wetting time and water absorption ratio reported the use of a piece of double folded tissue paper placed in a Petri dish containing 6 ml of water. One tablet was placed on this paper and the time for complete wetting of tablet was noted as wetting time. The wetted tablet was then weighed and the water absorption ratio, R, was determined according to equation.
R = 100 (W a −W b ) /W b
W b and W a are the weights of tablet before and after water absorption
The tablet tensile strength is the force required to break a tablet by compressing it in the radial direction and is measured using a tablet hardness tester.
Monsanto hardness tester Phyzer type hardness tester
MOISTURE UPTAKE TEST
The test can be carried out by keeping ten tablets along with calcium chloride in a desiccator maintained at 37 °C for 24 hrs to ensure complete drying of the tablets.
The tablets are then weighed and exposed to 75% RH, at room temperature for 2 weeks. The required humidity can be achieved by keeping saturated sodium chloride solution in the dessicator for 24 hrs.
The tablets are reweighed and the percentage increase in weight is recorded. If the moisture uptake tendency of a product is high, it requires special dehumidified area for manufacturing and packing.
MEASUREMENT OF TABLET POROSITY
The mercury penetration porosimeter can be used to measure the tablet
porosity which is a relative assessment of the degree of water penetration in
the formulation, responsible for its fast disintegration.
IN-VITRO DISPERSION TIME
The test is performed by placing two tablets in 100 ml water and stirring it gently, till the tablets get completely disintegrated.
The formulation is considered to form a smooth dispersion if the complete dispersion passes through a sieve screen with a nominal mesh aperture of 710 μm without leaving any residue on the mesh.
IN-VITRO DISINTEGRATION TEST
This test are carried out by using any one of the following method
Tablet disintegration apparatus
Modified dissolution apparatus (as per J.Pharm)
Disintegration Test on Shaking Water Bath
Disintegration Test with Rotary Shaft Method
Disintegration Test using Texture Analyzer
Disintegration Test using Electro Force
Apparatus with wire basket in a beaker.
DISINTEGRATION USING TEXTURE ANALYZER
The in vitro disintegration behavior of fast dissolving systems manufactured by the main commercialized technologies was studied using the texture analyzer (TA) instrument.
IN-VITRO DISSOLUTION STUDY
The dissolution method for oral disintegrating tablets is the same as that of conventional tablets.
USP 2 paddle apparatus is most suitable and common choice for dissolution test of oral disintegrating tablets, where the paddle speed is 50 rpm is used.
The USP 1 (basket) apparatus may have certain application for such tablets but is used less, frequently due to specific physical properties of tablets.
Specifically tablet fragments or disintegrating tablet masses become trapped on the inside top of the basket spindle where little or no effective stirring occurs, yielding irreproducible results in dissolution profiles.
ODTs can offer several biopharmaceutical advantages over conventional solid dosage forms such as,
Require small amount of the drug to be effective
Offer better drug bioavailability
ODTs may be suitable for oral delivery of drugs such as proteins and peptide based therapeutics that has limited bioavailability when administered by conventional tablets.
Because drugs delivered in ODTs may be absorbed in the pre gastric sites of highly permeable buccal and mucosal tissues of the oral cavity, they may be suitable for delivering relatively low-molecular weight and highly permeable drugs .
Orally disintegrating tablets (FDTs) have better patient acceptance and compliance and may offer improved biopharmaceutical properties, improved efficacy, and better safety compared with conventional oral dosage forms.
Prescription FDT products initially were developed to overcome the difficulty in swallowing conventional tablets with water among pediatric, geriatric, and psychiatric patients with dysphagia.
Future possibilities for improvements in FDTs and drug delivery are bright, but the technology is still relatively new.
1. International journal of research in Ayurveda and Pharmacy.
2. Journal of Chemical and Pharmaceutical Research, 2009, 1(1): 336-341.
3. The Indian Pharmacist, Volume 3, Issue 19, p.72-75 (2004).
4. United States Pharmacopoeia 24/NF 19. The Official Compendia of Standards. Asian ed. Rockville, MD: United States Pharmacopoeial Convention Inc; 2000:1913-1914.
5. Bentham science Publishers- Recent patents on Drug delivery and Formulations, Volume 4, Number 3, November 2010.
6. Aulton’s Pharmaceutics- The design and manufacture of medicines, Edited by Michael E.Aulton- 3 rd Edition, 2008.
7. FDA, Guidance for Industry: Orally Disintegrating Tablets Draft Guidance , (Rockville, MD, April 2007).
8. Review article- Recent Patents and Trends in Orally Disintegrating Tablets by Farhan A. AlHusban, Amr M. El-Shaer, Rhys J. Jones and Afzal R. Mohammed