Pharmaceutical and Economical Aspects of Porous Tablets

Deepak Prashar*¹, Sanjay Kumar², Abhishek Chauhan¹, Rahul Purohit¹

¹Department of Pharmaceutical Sciences, Manav Bharti University, Solan (H.P.), India

²Department of Economics, Govt. College Dharampur, Mandi (H.P.), India

ABSTRACT:

Porous tablets are solvent less disintegrating oral dosages form which is being widely accepted in the pharmaceutical world. Various conventional and patented techniques are available for the formulation of porous tablets. The economical aspects of the porous tablets along with its worldwide market is being studied and reviewed.

KEYWORDS: porous tablets, economical aspects, patented techniques, world market

INTRODUCTION:

Porous tablets are oral solid dosage forms that disintegrate in the oral cavity in easy swallow residue¹. Porous tablets are also called as orodispersible tablets, fast disintegrating tablets (FDT), orally disintegrating tablets (ODT), quick disintegrating tablets, mouth dissolving tablets, rapid dissolving tablets, quick melt tablets and rapid melt tablets ^2-4. Porous tablets have started gaining popularity and acceptance as new drug delivery systems. The merits of porous tablets are their easy administration and better patient compliance especially in geriatrics and pediatrics. These dosages foam requires fast dissolution in the mouth, hence they are made of either very porous and soft‐ moulded matrices or compressed into tablets with very low compression force. However, this makes the tablets friable or brittle, which often requiring specialized peel‐off blister packaging.

The Porous tablets are also designated as freeze-dried wafer. It is a quick-dissolving, thin matrix that contains an active pharmaceutical agent that does not need water for swallowing. To ensure physical stability this fragile dosage form requires unit-dose packaging. The wafer disintegrates instantaneously in the buccal cavity and releases drug, which dissolves in the saliva. The saliva is swallowed and the drug is absorbed across the gastrointestinal tract (GIT)⁵. Table 1 enlisted the research work carried out on porous tablets by various researchers in last few decades.

Table 1: Work Carried Out on Porous Tablets in Last Few Decades

S. No.	Research on porous tablets	References
1.	Development and evaluation of glyburide fast dissolving tablets using solid dispersion technique.	Valleri et al.^6
2.	Formulations and bioavailability of propyphenazone in lyophilized tablets	Gafitanu et al.^7
3.	Acetaminophen flashtab formulation: fast disintegration and optimal absorption of the active ingredient	Bruna et al.^8
4.	Double-blind crossover study of the efficacy and acceptability of oxazepam expidet tablets compared to placebo in patients undergoing gynaecological surgery	Brampton and Plantevin^9
5.	The use of temazepam expidet as a pre-medicant in children	Schroeder^10
6.	Temazepam in fast dispensing dosage form as a pre-medication for children	Smith et al.^11
7.	A gamma scintigraphic study to compare esophageal clearance of expidet formulations, tablets and capsules in supine volunteers	Wilson et al.^12
8.	A gamma scintigraphic study of gastric coating by expidet tablet and liquid formulations	Washington et al.^13
9.	The behaviour of a fast-dissolving dosage form (Expidet) followed by gscintigraphy	Wilson et al.^14
10.	Dissolution testing of orally disintegrating tablets	Klancke^15
11.	Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity	Bi^16
12.	Evaluation of rapidly disintegrating tablets prepared by direct compression method	Bi^17
13.	Evaluation of disintegration testing of different fast dissolving tablets using texture analyzer	El-Arini and Clas^18

TECHNIQUES OF POROUS TABLETS PREPRATION:

Several technologies have been developed on the basis of formulation aspects and different processes and resulting dosage forms vary on several parameters like mechanical strength, porosity, dose, stability, taste, dissolution rate and overall bioavailability.

Table 2: Porous Tablet Manufacturing Processes

Wet granulation^19	Milling and mixing of drugs and excipients. Preparation of binder solution. Wet massing by addition of binder solution or granulating solvent. Screening of wet mass followed by drying of the wet granules. Screening of dry granules. Blending with lubricant and disintegrant to produce “running powder” Compression of tablet
Dry granulation	Milling and mixing of drugs and excipients Compression into slugs or roll compaction Milling and screening of slugs and compacted powder Mixing with lubricant and disintegrant Compression of tablet
Direct compression^20	Milling and mixing of drugs and excipients Compression of tablet
Cotton candy Process^21	Involves the formation of matrix of polysaccharides by simultaneous action of flash melting and spinning. This candy floss matrix is then milled and blended with active ingredients and excipients after re-crystallization and subsequently compressed to porous tablets.
Mass Extrusion^22	Involves softening the active blend using the solvent mixture of water soluble polyethylene glycol, methanol and expulsion of softened mass through the extruder or syringe to get a cylindrical shape of the product into even segments using heated blade to form tablets.
Sublimation^23	Inert solid ingredients that volatilize rapidly like urea, camphor ammonium carbonate, ammonium bicarbonate, and hexamethylenetetramine were added to the other tablet ingredients and the mixture is compressed into tablets. The volatile materials were then removed via sublimation, which generates porous structure.
Molding^24	Water-soluble ingredients with a hydro alcoholic solvent is used and is molded into tablets under pressure lower than that used in conventional tablet compression.
Freeze Drying/ Lyophilization^25	The drug is dissolved or dispersed in an aqueous solution of a carrier. The mixture is poured into the wells of the preformed blister packs. The trays holding the blister packs are passed through liquid nitrogen freezing tunnel to freeze the drug solution. Then the frozen blister packs are placed in refrigerated cabinets to continue the freeze drying. Finally the blisters are packaged and shipped.
Disintegrant Addition^26-27	Involves the addition of superdisintegrants in optimum concentration to the formulation to achieve rapid disintegration/dissolution
Nanonization^28	Involves size reduction of drug to nanosize by milling the drug using a proprietary wet-milling technique. The nanocrystals of the drug are stabilized against agglomeration by surface adsorption on selected stabilizers, which are then incorporated

There are several patented techniques for the preparation of porous tablets. All these patented techniques involve specific formulation processes²⁹.

· Zydis, Quicksolv, Flashtab involves Lyophilization

· Durasolv, Ziplet, Fast melt is based on Moulding

· Lyoc, Orasolv, Wow tab, Rapi tab utilizes Multiparticulates³⁰ Compressed tablets processes

· Advatab, Oraquick captilises on Micromask taste Masking and Microcaps³¹/diffuscap CRTechnology

· FlashDose is processed by Cotton-candy process

These are among few patented techniques being available in literature. These techniques have several merits and at the same time certain demerits. The basic demerit of these techniques is that they are expensive and as a result of that it affects the economy. The economic aspects of these techniques are the prior important factor followed by other mechanical and biological aspects. Many different drugs are being successfully formulated into the porous tablets dosages forms.

Table 3: Enlisted Drugs Being Available As Porous Tablets Form^32-33

S. No.	Active Ingredient	Manufacturer	Trade Name
1.	Piroxicam	Pfizer Inc., NY, USA	Felden fast melt
2.	Loratidine	Schering plough Corp., USA	Claritin redi Tab
3.	Rizatriptan	Merck and Co., NJ, USA	Maxalt MLT
4.	Olanzapine	Eli lilly, Indianapolis, USA	Zyprexia
5.	Famotidine	Merck and Co., NJ, USA	Pepcid RPD
6.	Ondansetron	Glaxo Wellcome, Middlesex, UK	Zofran ODT
7.	Zolmitriptan	AstraZeneca, Wilmington, USA	Zoming-ZMT
8.	Selegilline	Amarin Corp., London, UK	Zeplar TM
9.	Acetaminophen	Bristol myers Squibb, NY, USA	Tempra Quiclets
10.	Paracetamol	Prographarm, Chateauneuf, France	Febrectol
11.	Nimesulide	Panacea Biotech, New delhi , India	Nimulid MDT
12.	Rofecoxib	Torrent pharmaceuticals , India	Torrox MT
13.	Olanzapine	Ranbaxy lab. Ltd. New-Delhi, India	Olanex instab
14.	Montelukast	Ranbaxy lab. Ltd. New-Delhi, India	Romilast
15.	Diphenhydramine and pseudoephedrine	Warner Lambert, NY, USA	Benadryl Fastmelt
16.	Cisapride monohydrate	Janssen pharmaceutics	Propulsid Quicksolv
17.	Risperidone	Janssen pharmaceutics	Risperdal MTab
18.	Phloroglucinol Hydrate	Farmalyoc	Spasfon Lyoc)
19.	Ibuprofen	Ethypharm	Nurofen FlashTab)
20.	Paracetamol	Cima Labs,Inc.	Tempra Quicklets
21.	Zolmitriptan	Cima Labs,Inc.	Zolmig Repimelt
22.	Hyoscyamine Sulfate	Cima Labs, Inc.	(NuLev
23.	Famotidine	Yamanouchi Pharma Tech. Inc.	Gaster D)
24.	Ibuprofen	Eurand International	Cibalgina DueFast
25.	Tramadol HCl	Fuisz Technology, Ltd.	Relivia Flash dose
26.	Hyoscyamine Sulfate	KV Pharm.Co.,Inc.	Hyoscyamine Sulfate ODT
27.	Aripiprazole	Otsuka America/Bristol-Myers Squibb	Abilify Discmelt
28.	Fexofenadine	Sanofi Aventis	Allegra ODT
29.	Donepezil	Eisai Co.	Aricept ODT
30.	Desloratadine	Schering-Plough	Clarinex RediTabs
31.	Loratadine	Wyeth	Alavert Quick Dissolving Tablets
32.	Clonazepam	Par Pharmaceutical	Clonazepam ODT
33.	Clozapine	AzurPharma	FazaClo
34.	Acetaminophen	McNeil Consumer Healthcare	Jr. Tylenol Meltaways
35.	Clonazepam	Roche	Klonopin Wafers
36.	Loratadine	Ranbaxy	Loratadine Redidose
37.	Mirtazapine	Teva Pharmaceuticals	Mirtazapine ODT
38.	Alprazolam	Schwarz Pharma	Niravam
39.	Ondansetron	Teva Pharmaceuticals	Ondansetron ODT
40.	Prednisolone	Sciele Pharma	Orapred ODT
41.	Carbidopa/levodopa	Schwarz Pharma	Parcopa
42.	Lansoprazole	Takeda Pharmaceuticals	Prevacid SoluTab
43.	Mirtazapine	Schering-Plough	Remeron SolTab
44.	Risperidone	Janssen	Risperdal M-Tab
45.	Diphenhydramine	Chattem	UNISOM SleepMelts
46.	Zolmitriptan	AstraZeneca	Zomig-ZMT
47.	Olanzapine	Eli Lilly and Company	Zyprexa Zydis
48.	Citalopram	Biovail	Citalopram ODT
49.	Metoclopramide	Salix Pharmaceuticals	Metoclopramide Zydis
50.	Metoclopramide	Schwarz Pharma	Reglan ODT
51.	Tramadol/Acetaminophen	Biovail	Tramadol/Acetaminophen ODT
52.	Zolpidem	Biovail	Zolpidem ODT

WORLD MARKET SCENARIO OF POROUS TABLETS:

Today world pharmaceutical market is flooded with the number of tablets and other oral dosages forms. Porous tablets or ODT have grabbed the major portion of this market. The fast disintegration rate and solvent less disintegration makes this oral dosages form acceptable all over the world and among all categories of consumers. Among the two major supplying countries of the porous tablets India ranks on top followed by China. Figure 1 represents the share of two dominating countries in the field of porous tablets by a pie diagram. The other countries too are actively participating in this field but their share is negligible in comparison to India and China. India has an estimated 21 major suppliers (61.76%) of porous tablets in the world pharmaceutical market whereas China has 13 major suppliers (38.24%).

Fig 1: Share of two dominating Porous tablets manufacturers

ECONOMIC PROSPECTIVE OF POROUS TABLETS:

Illness will remains with human life. Now these days medical science has made remarkable progress in the field of medicines. In the present time of throat cut competition developing new drug delivery technologies and utilizing them in product development is critical for pharmaceutical companies to survive.

Fig 2: Porous tablet market scenario

Fig 3: Oral tablets market scenario

This applies to all pharmaceutical companies, regardless of their size. FDT have received ever increasing demand during the last decade and the field has become a rapidly growing area in the pharmaceutical industry. FDT overcome the disadvantages of conventional dosage form (tablets & capsules) especially difficulty in swallowing in paediatric and geriatric patient³⁴.The global market for MDT in the year 2004 was estimated as $ 2.4 billion, which was increased to $ 4.56 billion in the year 2010 and would surely increase in near future because of its rapid acceptance by consumer and pharmaceutical companies³⁵.

The oral drug delivery market³⁶ was estimated to be worth $24 billion in 2004 and forecast to reach $ 52 billion by 2010 with a CAGR of this FDDT, taste; masked &micro emulsion formulation segments constitute a 22% share with an expected CAGR of 17% of 2010. In today’s market world consumer satisfaction is most important consideration and industries are trying continuously to achieve this objective. An extension of market exclusivity, which can be provided by a fast-dissolving/disintegrating dosage form, leads to increased revenue, while also targeting underserved and under-treated patient populations. Although the cost to manufacture these specialized dosage forms exceeds that of traditional tablets, this additional cost is not being passed on to the consumer.

CONCLUSION:

These porous tablets form provides benefit over the conventional dosage form by reducing the difficulty of swallowing by paediatric and geriatric patient. The merits of patented techniques could be applied to increase the pharmaceutical utilization of this dosage form. These possibilities of modifications and advancement has made this dosages form to cement its place in today’s ever changing environment. The economic aspect of porous tablets and world market scenario clearly indicates its popularity and acceptance rate among the consumer. Moreover the market of this oral dosage form has a bright future ahead.

REFERENCES:

1. Sreenivas SA. Orodispersible tablets: New‐ fangled drug delivery system‐ A Review. Ind. J. Pharm. Educ. Res. 2005; 39(4): 177‐81.

2. Suresh B, Rajendar KM, Ramesh G and Yamsani MR. Orodispersible tablets: An overview. Asian J. Pharm. 2008; 2: 2-11.

3. Fu Y, Yang S, Jeong SH, Kimura S and Park K. Orally fast disintegrating tablets: Developments, technologies, taste-masking and clinical studies. Critical reviews in therapeutic drug carrier systems 2004; 21(6): 433-76.

4. Bandari S, Mittapalli RK, Gannu R and Rao YM. Orodispersible tablets: An overview. Asian J. Pharm. 2008; 2(1): 2.

5. Dobetti L. Fast-melting tablets: Developments and technologies. Pharm. Tech. 2000; 12(9): 32-42.

6. Valleri M, Mura P, Maestrelli F, Cirri M and Ballerini R. Development and evaluation of glyburide fast dissolving tablets using solid dispersion technique. Drug Dev. Ind. Pharm. 2004; 30(5): 525-34.

7. Gafitanu E, Dumistracel I and Antochi S. Formulations and bioavailability of propyphenazone in lyophilized tablets. Rev. Med. Chir. Soc. Med. Nat. Iasi. 1991; 95 (1–2): 127–128.

8. Bruna E, Leneveu A, Abouchaera ML, Delhotal B, Chauveau C, Rayot F and Fouvat B. Acetaminophen flashtab formulation: fast disintegration and optimal absorption of the active ingredient. Proc. Intl. Symp. Cont. Rel. Bioact. Mater. 1998; 25: 938–939.

9. Brampton WJ and Plantevin OM. Double-blind crossover study of the efficacy and acceptability of oxazepam expidet tablets compared to placebo in patients undergoing gynaecological surgery. Int. Med. Res. 1985; 13 (3): 169–173.

10. Schroeder HG. The use of temazepam expidet (FDDF) as a pre-medicant in children. Acta. Psychiatr. Scand. Suppl. 1986; 332: 167–171.

11. Smith GB, Huges DG and Kumar V. Temazepam in fast dispensing dosage form as a pre-medication for children. Anaesthesia 1985; 40: 368–371.

12. Wilson CG, Washington N, Norman S, Greaves JL, Peach JM and Pugh K. A gamma scintigraphic study to compare esophageal clearance of expidet formulations, tablets and capsules in supine volunteers. Int. J. Pharm. 1988; 46: 241–246.

13. Washington N, Wilson CG, Greaves JL, Norman S, Peach JM and Pugh K. A gamma scintigraphic study of gastric coating by expidet tablet and liquid formulations. Int. J. Pharm. 1989; 57: 17–22.

14. Wilson CG, Washington N, Peach J, Murray GR and Kennerley J. The behaviour of a fast-dissolving dosage form (Expidet) followed by gscintigraphy. Int. J. Pharm. 1987; 40:119–123.

15. Klancke J. Dissolution testing of orally disintegrating tablets. Dissolution Technol. 2003; 10(2): 6-8.

16. Bi Y. Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity. Chem. Pharm. Bull. 1996; 44: 2121-2127.

17. Bi Y. Evaluation of rapidly disintegrating tablets prepared by direct compression method. Drug Dev. Ind. Pharm. 1999: 25(5): 571-581.

18. El-Arini SK and Clas SD. Evaluation of disintegration testing of different fast dissolving tablets using texture analyzer. Pharm. Dev. Technol. 2002; 7(3): 361-371.

19. Liang L, Bhatt PP and Wang H. US20080131501A1 (2008).

20. Namdev K and Gour M. W007074472A2 (2007).

21. Fuisz RC. US4855326 (1989).

22. Sherry R. US20080085308 (2008).

23. Koizumi K. New method of preparing high porosity rapidly saliva soluble compressed tablets using mannitol with camphor, a subliming material. Int. J. Pharm. 1997; 152: 127-131.

24. Paulsen NE, Johnson R and Coffee M. US20080075759 (2008).

25. Hamed E, Hillman L, Khankari RK, Moe D and Nguyen T. US20080031947 (2008).

26. Mezaache N, Frisdee SE, Woodall PB and Herman MR. US20030124184A1 (2003).

27. Staniforth J. US20020068084 (2002).

28. Liversidge GG, Engers DA, Roberts ME, Ruddy SB, Wong S and Xu S. US20006045829 (2000).

29. Modi A and Tayade P. Enhancement of dissolution profile by solid dispersion (kneading) technique. AAPS Pharm. Sci. Tech. 2006, 7(3): 68-72.

30. Siebert JM, Khankari RK, Kositprapa U and Pather I. EP1104288A4 (2003).

31. Misra TK, Currington JW, Montwill BK, Satish V, Sanghvi PP, Sisak JR and Raiden M. US20006048541 (2000).

32. Sammour OA, Hammad MA and Megrab NA. Formulation and Optimization of Mouth Dissolve Tablets Containing Rofecoxib Solid Dispersion. AAPS Pharm. Sci. Tech. 2006; 7(2): 162-69.

33. Fini A, Bergamante V, Ceschel GC and Ronchi C. Fast dispersible/slow releasing ibuprofen tablets. Eur. J. Pharm. Biopharm. 2008; 69: 335–41.

34. Puttalingaiah L, Kavitha K and Mani T. Fast Disintegrating tablets: An overview of formulation, technology and evaluation. Res. J. Pharm. Chem. Bio. Sci. 2011; 2(2): 589-601.

35. Arnum VP. Outsourcing Solid Dosage Manufacturing. Pharm. Technol. 2006; 30(6): 44-52.

36. Bhowmik D, Chiranjib, Jaiswal J, Dubey V and Chandira M. Fast dissolving tablet: A review on revolution of novel drug delivery system and new market opportunities. Der Pharmacia Lettre 2009, 1 (2): 262-276.

Received on 10.12.2011

Accepted on 23.01.2012

© A&V Publication all right reserved

Research Journal of Pharmaceutical Dosage Forms and Technology. 4(1): Jan. - Feb., 2012, 19-23