Medicated Chewing Gum: New Reformulation Technique

Sponsored Links

Image

Medicated Chewing Gum (MCG) is a novel drug delivery system containing masticatory gum base with pharmacologically active ingredient and intended to use for local treatment of mouth diseases or systemic absorption through oral mucosa. MCG is considered as vehicle or a drug delivery system to administer active principles that can improve health and nutrition. The present article reviews MCG Drug Delivery System concepts including its merits and demerits.

INTRODUCTION:

Pharmacological Active Agents or Drugs are formulated into variety of
dosage forms like Tablets, Capsules, Injectables, Inhalers, Ointments etc considering
Physicochemical properties, Pharmacokinetic & Pharmacodynamic parameters
and Biopharmaceutical aspects of Drugs. In addition to its confectionary role,
Chewing Gum (CG) also has proven value as a delivery vehicle for pharmaceutical
and nutraceutical ingredients1. Today CG is convenient drug delivery
system which is appropriate for a wide range of active substances2.
Many therapeutic agents are absorbed in the oral cavity. For the drugs having
significant buccal absorption, dosage forms such as Lozenges, Chewable tablets
and Chewing Gum permits more rapid therapeutic action compared to per-oral dosage
forms3. Chewable tablets and chewing gum have been very well received
by the parents for use in children with full dentition. Children in particular
may consider chewing gum as a more preferred method of drug administration compared
with oral liquids and tablets. The use of MCG is feasible in local treatment
of diseases of oral cavity as well as treatment of systemic conditions.

Chewing gum has been used for centuries to clean the mouth and freshen the breath4. The first patent for the production of chewing gum was filed in 1869 and was issued to Mr. W. F. Semple in Ohio under U. S. Patent No. 98,304. A MCG containing Acetyl Salicylic Acid was commercially introduced in 19285. In 1991, Chewing Gum was approved as a term for pharmaceutical dosage form by the commission of European Council.

MCGs are solid, single dose preparations with a base consisting mainly of gum that are intended to be chewed but not swallowed. They contain one or more active substances which are released by chewing and are intended to be used for local treatment of mouth diseases or systemic delivery after absorption through the buccal mucosa6.

Moreover there is need of reformulation of existing drug into New Drug Delivery Systems (NDDS) to extend or protect product patents thereby delaying, reducing or avoiding generic erosion at patent expiry. To provide additional patient benefit, meet competitive challenges and to conserves revenues, the research on NDDS is gaining importance now a day. MCG is one of them.

Owing to new social and behavioral trends in the past modern age, such as the growing consumer health awareness and increasing attention to safety products, chewing gum has been known for a new image and potential. Chewing gum today is gaining consideration as a vehicle or a delivery system to administer active principles that can improve health and nutrition.

MCG represents the newest system with potential uses in pharmaceuticals, over the counter medicines and neutraceuticals7. The drugs intended to act in oral cavity often have low water/saliva solubility and chewing gum constitute a valuable delivery system for such drugs.

MERITS OF MCG:

1. Dose not requires water to swallow. Hence can be taken anywhere1.

2. Advantageous for patients having difficulty in swallowing5.

3. Excellent for acute medication.

4. Counteracts dry mouth, prevents candidiasis and caries1.

5. Highly acceptable by children.

6. Avoids First Pass Metabolism and thus increases the bioavailability of drugs5.

7. Fast onset due to rapid release of active ingredients in buccal cavity and subsequent absorption in systemic circulation1.

8.Gum does not reach the stomach. Hence G.I.T. suffers less from the effects of excipients.

9. Stomach does not suffer from direct contact with high concentrations of active principles, thus reducing the risk of intolerance of gastric mucosa5.

10.Fraction of product reaching the stomach is conveyed by saliva delivered continuously and regularly. Duration of action is increased.

11.Aspirin, Dimenhydrinate and Caffeine8 shows faster absorption through MCG than tablets.

DEMERITS OF MCGS:

1. Risk of over dosage with MCG compared with chewable tablets or lozenges that can be consumed in a considerable number and within much shorter period of time4.

2.Sorbitol present in MCG formulation may cause flatulence, diarrhea9.

3.Additives in gum like flavouring agent, Cinnamon can cause Ulcers in oral cavity and Licorice cause Hypertension.

4.Chlorhexidine oromucosal application is limited to short term use because of its unpleasant taste and staining properties to teeth and tongue10.

5.Chewing gum have been shown to adhere to different degrees to enamel dentures and fillers11.

6.Prolong chewing on gum may result in pain in facial muscles and earache in children. 12.

COMPONENTS OF MCG:

Chewing gum is a mixture of natural or synthetic gums and resins, sweetened with sugar, corn syrup, artificial sweetners and may also contain colouring agents and flavour. The basic raw material for all CG is natural gum Chicle, obtained from the sapodilla tree4. Chicle is very expensive and difficult to procure therefore other natural gum or synthetic materials like polyvinylacetate and similar polymers can be used as gum base.

Typically Chewing Gum comprises two parts

1.Water insoluble chewable gum base portion13

2.Water-soluble bulk portion13

1. Water insoluble gum base generally comprises Elastomers, Resins, Fats and Oils, and Inorganic fillers5,13.

a) Elstomers: Elastomer provides elasticity and controls gummy texture.

Natural elastomer: Natural rubbers like Latex or Natural gums such as Jelutong, Lechi Caspi, Perillo, Chicle.

b) Plastisizers: These are used to regulate cohesiveness of product. These are again divided into Natural and Synthetic.

Natural Plastisizers include Natural rosin esters like Glycerol Esters or Partially hydrogenated Rosin, Glycerol Esters of Polymerized Esters, Glycerol Esters of Partially dimerized Rosin & Pentaerythritol Esters of Rosin.

Synthetic Plastisizers include Terpene Resins derived from α-pinene and/or d-limonene.

c) Fillers or Texturizers: Provide texture, improve chewability, provide reasonable size of the gumlump with low dose drug. Commonly used fillers are Magnesium and Calcium Carbonate, Ground Limestone, Magnesium and Aluminium Silicate, Clay, Alumina, Talc, Titanium Oxide & Mono/ di/ tri Calcium Phosphate.

2. Water soluble portions contains Bulk Sweetners, High intensity Sweetners, Flavouring agents, Softners, Emulsifiers, Colours & Antioxidants.

a) Softners and Emulsifiers: These are added to the chewing gum in order to optimize the chewability and mouth feel of the gum. Softners include Glycerin, Lecithin, Tallow, Hydrogenated Tallow, Mono/ di/ tri-Glycerides, Fatty acids like Stearic acid, Palmitic acid, Oleic acid and Linoleic acid.

b) Colourants and Whiteners may include FD & C type dyes and lakes, fruit and vegetable extracts, Titanium Dioxide.

c) Sweetners: These are of two types, Aqueous and
Bulk.

Aqueous Sweetners can be used as softners to blend the ingredients
and retain moisture. These include Sorbitol, hydrogenated Starch hydrolysates
and Corn Syrups. Corn syrup keeps gum fresh and flexible.

Bulk Sweetners include Sugar and Sugarless components. Sugar
Components include Saccharides like Sucrose, Dextrose, Maltose, Dextrin, Fructose,
Galactose, Corn Syrup. Sugarless Components include sugar alcohols
such as Sorbitol, Manitol, Xylitol, hydrogenated Starch hydrolysate. High intensity
artificial Sweetners can also be included to provide longer lasting sweetness
and flavour perception e.g. Sucralose, Aspartame, salt of Acesulfame, Alitame,
Saccharin, Glycerrhizin, Dihydrochalcones.

d) Bulking agents: These are used if low calorie gum is desired. Examples of low caloric bulking agents include Polydextrose, Oligofructose, Inulin, Fructooligosaccharides, Guargum hydrolysate, Indigestible Dextrin.

e) Flavouring Agents: A variety of flavouring agents are used to improve flavour in chewing gum includes essential oils, such as Citrus oil, fruit essences, Peppermint oil, Spearmint oil, Mint oil, Clove oil & Oil of Wintergreen. Artificial flavouring agents can also be used.

f) Active Component: In medicated chewing gum active pharmacological agent may be present in core or coat or in both. The proportion of which may vary from 0.5-30% of final gum weight. A small, unionized, lipophilic and enzymatically stable active agent is likely to be absorbed more readily. A saliva soluble ingredient will be completely released within 10-15 minutes of chewing whereas lipid soluble ingredient will dissolve in the gum base and thereafter be slowly and completely absorbed.

MCG consists of masticatory gum core that may be coated. The core is composed of an aqueous insoluble gum base which can be mixed with Sweetners and Flavours. The coating can be applied as a film of polymers, waxes, sweetners, flavours and colour or a thick layer of sugar or sugar alcohol. The optimal properties of active ingredient in MCG are shown in Table 1.

Table 1: Optimal Properties of Drug4

Physicochemical Properties of Drug High Salivary Solubility
pH independent solubility
Tasteless
Patient Related Factors Non-toxic to oromucosa and salivary ducts
Non-carcinogenic
Should not cause tooth decay
Should not cause oromucosa and teeth staining
Should not affect salivary flow rate

MANUFACTURING PROCESSES:

Different methods employed for the manufacturing of CG can be broadly
classified into three main classes namely.

1.Conventional/ traditional Method (Melting).

2.Freezing, grinding and tabletting Method.

3.Direct Compression Method

1.Conventional/ traditional Method3:

Components of gumbase are softened or melted and placed in a kettle mixer to which sweetners, syrups, active ingredients and other excipients are added at a definte time. The gum is then sent through a series of rollers that form into a thin, wide ribbon. During this process, a light coating of finely powdered sugar or sugar substitutes is added to keep the gum away from sticking and to enhance the flavour. In a carefully controlled room, the gum is cooled for upto 48 hours. This allows the gum to set properly. Finally the gum is cut to the desired size and cooled at a carefully controlled temperature and humidity.

Limitations14:

1.Elevated temperature used in melting restrict the use of this method for thermo labile drugs.

2.Melting and mixing of highly viscous gum mass makes controlling of accuracy and uniformity of drug dose difficult.

3.Lack of precise form, shape or weight of dosage form.

4.Technology not so easily adaptable to incorporate the stringent manufacturing conditions required for production of pharmaceutical products.

5.Such a chewing gum composition is difficult to form into chewing gum tablets becauseof their moisture content (2-8%). If attempted to grind and tablet such a composition would jam the grinding machine, stick to blades, screens adhere to punches and would be difficult to compress.

2. Cooling, Grinding and Tabletting Method3,15:

This method has been developed with an attempt to lower the moisture content and alleviate the problems mentioned in conventional method.

Cooling and Grinding:

The CG composition (base) is cooled to a temperature at which the composition is sufficiently brittle and would remain brittle during the subsequent grinding step without adhesion to the grinding apparatus. The temperature required for cooling is determined in part by the composition of the CG and is easily determined empirically by observing the properties of the cooled chewing gum composition. Generally the temperatures of the refrigerated mixture is around -15oC or lower. Amongst the various coolants like liquid nitrogen, hydrocarbon slush use of solid carbon dioxide is preferred as it can give temperatures as low as -78.5oC, it sublimes readily on warming the mixture, is not absorbed by the chewing gum composition, does not interact adversely with the processing apparatus and does not leave behind any residue which may be undesirable or potentially hazardous.

The refrigerated composition is then crushed or ground to obtain minute fragments of finely ground pieces of the composition.

Alternatively, the steps of cooling the chewing gum composition can be combined into a single step. As an example, cooling the grinding apparatus itself which can be done by contacting the grinding apparatus with a coolant or by placing the grinding apparatus in a cooling jacket of liquid nitrogen or other cold liquid. For more efficient cooling, the chewing gum composition can be pre cooled prior to cooling to the refrigeration temperature.

Sometimes a mixture of chewing gum composition, solid carbon dioxide and precipitated silica is ground in a mill grinder in a first grinding step. Additional solid carbon dioxide and silica are added to the ground composition, and the composition is further ground in a second grinding step. This two step grinding process advantageously keep the chewing gum composition at a very low temperature. The presence of solid carbon dioxide also serves to enhance the efficiency of the grinding process. The same process can be made multiple by adding incorporating additional carbon dioxide and/or precipitated silica at each step.

Certain additives can be added to the chewing gum composition to facilitate cooling, grinding and to achieve desired properties of chewing gum. These include use of anti-caking agent and grinding agent.

Use of anti-caking agent: An anti-caking agent such as precipitated silicon dioxide can be mixed with chewing gum composition and solid carbon dioxide prior to grinding. This helps to prevent agglomeration of the subsequently ground chewing gum particles.

Use of grinding agents: To prevent the gum from sticking to the grinding apparatus, 2-8% by weight of grinding aid such as alkaline metal phosphate, an alkaline earth metal phosphate or malto dextrin can be incorporated. However practical use of these substances is limited because these substances are highly alkaline and hence would be incompatible with acidic ionisable therapeutic agents. They also tend to remain in the composition and final chewing gum tablet and thus may be problematic for teharpeutic and safety point of view.

After the composition is ground to a powder, the coolant can be removed by allowing the coolant to evaporate. Alternatively it has been found that such a powdered mass when warmed to room temperature from the refrigerated state, they become cross linked or self adhere together to form an integrated body which incorporates minute air bubbles in the texture between the particles. This provides a chewing gum product that is light and gives a soft chewing impression when chewed.

· Tabletting:

Once the coolant has been removed from the powder, the powder can be
mixed with other ingredients such as binders, lubricants, coating agents ,sweeteners
etc, all of which are compatible with the components of the chewing gum base
in a suitable blender such as sigma mill or a high shear mixer. Alternatively
a Fluidized Bed Reactor (FBR) can be used. The use of FBR is advantageous as
it partially rebuilds the powder into granules, as well as coats the powder
particles or granules with a coating agent thereby minimizing undesirable particle
agglomeration. The granules so obtained can be mixed with antiadherents like
talc. The mixture can be blended in a V type blender, screened & staged
for compression. Compression can be carried out by any conventional process
like punching.

Limitation:

It requires equipment other than conventional tabletting equipment and requires careful monitoring of humidity during the tabletting process

3. Use of directly compressible chewing gum excipients16:

The manufacturing process can be accelerated if a directly compressible chewing gum excipient is available. The limitations of melting & freezing can be overcome by the use of these. PHARMAGUM®,is one such compactable gum system developed by SPI Pharma. Pharmagum is a mixture of polyol(s) & or sugars with a chewing gum base. It is available as directly compressible powder, free flowing powder which can be compacted into a gum tablet using conventional tablet press thus enabling rapid and low cost development of a gum delivery system. It is manufactured under CGMP conditions and complies with Food Chemicals Codex specifications as well as with FDA, so they can be considered as "Generally regarded as safe" (GRAS).

Pharmagum® is available in three forms namely S, M and C. Pharmagum® M has 50% greater gum base compared to Pharmagum®S. Pharmagum®S consists primarily of gumbase and sorbitol. Pharmagum®M contains gumbase, mannitol & Isomalt. Release of nicotine from directly compressible nicotine gum formulations and from Nicorette® prepared by conventional methods have shown that use of Pharmagum in formulation showed a faster release rate. Formulations made with Pharmagum® M & S are similar to tablet in appearance. Gums formed using compressible formulation are 10 times harder and crumble when pressure is applied resulting in faster release than conventional methods.

Use of Pharmagum S, M and C enables formulators to utilize a gum
delivery system quickly & more cost effectively than by traditional methods.

FACTORS AFFECTING RELEASE OF ACTIVE INGREDIENT:

1.Contact Time: The local or systemic effect is dependent on time of contact of MCG in oral cavity. In clinical trial chewing time of 30 minutes was considered close to ordinary use.

2.Physicochemical properties of active ingredient: Physicochemical properties of active ingredient plays very important role in release of drug from MCG. The saliva soluble ingredients will be immediately released within few minutes whereas lipid soluble drugs are released first into the gum base and then released slowly.

3.Inter individual variability: The chewing frequency and chewing intensity which affect the drug release from MCG may vary from person to person. In-vitro study prescribed by European Pharmacopoeia suggest 60 cycles per minute chewing rate for proper release of active ingredient6.

4.Formulation factor: Composition and amount of gum base affect rate of release of active ingredient. If lipophilic fraction of gum is increased, the release rate is decreased2.

SOME IMPORTANT FORMULATION ASPECT:

1.Increased amount of softners and emulsifiers in gum base fasten release whereas hard gum may retard2,4.

2.Cyclodextrin complexation or solubilisation technique increases aqueous solubility of drugs that are poorly water soluble17,18.

3.A solid system of lipophilic active ingredients bound to the cation exchange resin permits a sustained drug delivery system.

4.Microencapsulation or agglomeration are the methods to modify and control the release of active ingredient19,20.

{mospagebreak title=In-vitro drug release testing apparatus }

IN-VITRO DRUG RELEASE TESTING APPARATUS:

Number of apparatus for studying in-vitro drug release from medicated chewing gum has been developed.

An apparatus for in vitro drug release testing of medicated chewing gums has been developed by Kvist C et al21. They have studied the effect chewing surfaces, twisting movements of surfaces and temperature of test medium on release rate of drug from MCG.

Another novel dissolution apparatus has been developed for MCG by Rider JN et al22. The apparatus consist of conical Teflon base and a rotating, ribbed Teflon plunger suspended in a dissolution vessel. The rotation speed, plunger frequency, medium volume, medium type, medium sampling location, number of plunger ribs and number of gum pieces were studied by them.

In 2000, European Pharmacopoeia published a monograph describing a suitable apparatus for studying the in-vitro release of drug substances from MCG. The chewing machine consists of a temperature-controlled chewing chamber in which the gum piece is chewed by two electronically-controlled horizontal pistons driven by compressed air (Figure 1). The two pistons transmit twisting and pressing forces to the gum,while a third vertical piston, (“tongue”) operates alternately to the two horizontal pistons to ensure that the gum stays in the appropriate position. The temperature of the chamber can be maintained at 37±0.5°C and the chew rate can be varied. Other adjustable settings include the volume of the medium, the distance between the jaws and the twisting movement. The European Pharmacopoeia recommends using 20 ml of unspecified buffer (with a pH close to 6) in a chewing chamber of 40 ml and a chew rate of 60 strokes per minute6.

 

 

THERAPEUTIC USES OF MCG:

The use of sugar free gum to counteract dental caries by stimulation of saliva secretion has led to a more widespread use and acceptance of gums. It has been proved that chewing non-medicated chewing gums increases plaque pH, stimulates saliva flow and decrease decay23. MCGs containing Chlorhexidine for treatment of gingivitis and plaque has been available. The use of MCG in the treatment of oral infections has also been reported24. The active ingredient is released from the MCG and sufficient concentration is achieved in the oral cavity to prevent or treat local conditions of oral cavity.

CG is also useful delivery system for agents intended for systemic delivery. Drug that is released from gum within oral cavity can be absorbed via buccal mucosa. The MCGs can also be used as an alternative tool to buccal and sublingual tablets which are intended to act systemically because active ingredient is released more uniformly and cover greater area of absorption in oral cavity. Oral diseases are prevented or cured with MCG. MCGs for systemic effect in conditions like vitamin C deficiency25, pain & fever26, alertness27, motion sikness28, smoking cessation29, as well as for local effect in the conditions like plaque acid neutralization30, fresh breath23, disinfection31, anti-caries32, antiplaque33, antifungal34, antibacterial35 are available.

Fig. 2 indicates some examples of MCGs used in therapeutics.

 

 

a: Active pharmaceutical ingredient (Drug) EDTA: Ethylene diamine tetra-acetic acid

CONCLUSION:

The potential of MCG for buccal delivery, fast onset of action and the opportunity for product-line extension makes it an attractive delivery form. Reformulation of an existing product is required for patent protection, additional patient benefits and conservation of revenues.

REFERENCES:

1. Morjaria Y, Irwin WJ, Barnett PX, Chan RS and Conway BR: In Vitro Release of Nicotine From Chewing Gum Formulations. Dissolution Technologies, 12-15, May 2004.

2. http://www.fertin.com/fileadmin/pdf/Chewing_gum_as_a_DDS.pdf

3. Athanikar N.K., Gubler S. A: Process for manufacturing a pharmaceutical chewing gum. US Patent 6,322,828, 2001.

4. Jacobsen J., Christrup L.L., Jensen N-H: Medicated Chewing Gum: Pros and Cons. Am J Drug Deliv, 2 (2):75-88,2004.

5. Conway B.: Chewing Gum as a Drug Delivery System. The Drug Delivery Companies Report Autumn/Winter; 33-35, 2003.

6. European Pharmacopoeia. Strasbourg: European Directorate for the Quality of Medicines. Chewing Gums: Medicated. 5th ed., 260 & 601, 2004.

7. Lee W.W.: Chewing gum as a delivery vehicle for pharmaceutical and nutraceutical substances. Pharm Tech On-line, 2:1-11, 2001.

8. Kamimori GH, Karyekar CS, Otterstetter R, Cox DS, Balkin TJ, BelenkyGL, Eddington ND: The rate of absorption and relative bioavailability of caffeine

administered in chewing gum versus capsules to normal healthy volunteers. Int J Pharmaceutics, 234:159-167, 2002.

9. Goldberg LD, Ditchek NT: Chewing gum diarrhea. Am J Dig Dis, 23(6): 568,1978.

10. Addy M, Roberts WR: Comparison of the bisbiguanide antiseptics alexidine and chlorhexidine. II. Clinical and in vitro staining properties. J Clin Periodontol, 8(3):220-30, 1981.

11. Munksgaard EC, Nolte J, Kristensen K: Adherence of chewing gum to dental restorative materials. Am J Dent, 8(3):137-9, 1995.

12. Weil AT: Coca leaf as a therapeutic agent. Am J Drug Alcohol Abuse, 5(1): 75-86,1978.

13. Zyck D.J., Greenberg; M.J., Barkalow D.G., Marske S. W., Schnell P. G., Mazzone P.: Method of making coated chewing gum products containing various antacids. US Patent 6,645,535, 2003.

14. Cherukuri Subraman R., Bikkina Kirshnayya: Tabletted chewing gum composition and method of preparation. US Patent 4,753,805, 1988.

15. Mochizuki Keizo, Yokomichi Fumio: Process for the preparation of chewing gum.US Patent 4,000,321, 1976.

16. http://www.spipharma.com/ProductsFolder/120ParmaGum/120Pharmagum.html

17. Barabolak R.; Hoerman K.; Kroll N.: Chewing gum profiles in the US population. Community Dent Oral Epidemiol, 19:125-6, 1991.

18. Jacobsen J., Bjerregaard S., Pedersen M.: Cyclodextrin inclusion complexes of antimycotics intended to act in the oral cavity--drug supersaturation, toxicity on

TR146 cells and release from a delivery system. Eur J Pharm Biopharm,48(3):217-24, 1999.

19. Gudas V.V., Reed M. A., Schnell P. G., Tyrpin H..T., Russell M. P., Witkewitz D. L.: Method of controlling release of caffeine in chewing gum. US Patent 6,165,516,1998.

20. Yang Robert K.: Encapsulation composition for use with chewing gum and edible products. US Patent 4,740,376,1988.

21. Kvist C, Andersson SB, Fors S, Wennergren B, Berglund J.: Apparatus for studying in vitro release from medicated chewing gum. Int J Pharm, 189: 57-65,1999.

22. Rider JN, Brunson EL, Chambliss WG, Cleary RW, Hikal AH, Rider PH, Walker LA, Wyandt CM, Jones AB.: Development and evaluation of a novel dissolution apparatus for medicated chewing gum products. Pharm Res, 9: 255-60, 1992.

23. Imfeld T.: Chewing gum--facts and fiction: a review of gum-chewing and oral health. Crit Rev Oral Biol Med, 10(3):405-19, 1999.

24. Pedersen M, Rassing MR.: Miconazole chewing gum as a drug delivery system. Drug Dev Ind Pharm, 17(3): 411-20, 1991.

25. Christrup LL, Rasmussen SN, Rassing MR.: Chewing gum as a drug delivery system. Farmaci. Sci Ed,16: 44-47, 1988.

26. Woodford DW, LeskoLJ.: Relative bioavailability of aspirin gum. J Pharm Scie, 70(12):1341-1343, 1981.

27. Tyrpin HT, Russell MP, Witkewitz DL, Johnson SS, Ream RL, Corriveau CL.: Caffeine coated chewing gum product and process of making. US Patent: 6,444,241, 2002.

28. Seibel K, Schaffler K, Reitmeir P, Golly I.: A randomised, placebo-controlled study comparing two formulations of dimenhydrinate with respect to efficacy in motion sickness and sedation. Arzneimittelforschung, 52(7):529-36, 2002.

29. Silagy C, Lancaster T, Stead L, Mant D, Fowler G.: Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev, (3):CD000146, 2001.

30. Finn SB, Jamison HC.: The effect of a dicalcium phosphate chewing gum on caries incidence in children: 30-month results. J Am Dent Assoc, 74(5):987-95, 1967.

31. Smith AJ, Moran J, Dangler LV, Leight RS, Addy M.: The efficacy of an anti- gingivitis chewing gum. J Clin Periodontol, 23(1):19-23, 1996.

32. Oliveby A, Ekstrand J, Lagerlof F.: Effect of salivary flow rate on salivary fluoride clearance after use of a fluoride-containing chewing gum. Caries Res, 21(5): 393-401, 1987.

33. Etemadzadeh H.: Plaque-growth inhibiting effect of chewing gum containing urea hydrogen peroxide. J Clin Periodontol, 18(5): 337-40, 1991.

34. M Pedersen, MR Rassing: Miconazole and miconazolenitrate chewing gum as drug delivery system – a practical application of solid dispersion technique. Drug Dev Ind Pharm, 16(1):55-74, 1990.

35. Wertalik F, Bonorden R: Salivary levels of antibiotics from use of neomycin- gramicidin chewing troches. J Pharm Sci, 57(3):530-1, 1968.

Bumrela Shrinivas B.*1, Kane Rajesh N. 2, Dhat Shalaka P. 3

1Completed M. Pharm in Biopharmaceutics from Govt. College of Pharmacy, Karad in 2001. Dissertation topic: “Therapeutic Drug Monitoring of Phenytoin”. Worked as Principal for One year at College of Pharmacy, Medha. Presently working as Lecturer at Sinhgad Institute of Pharmaceutical Sciences, Lonavala.

Various papers are presented in Indian Pharmaceutical Congress (IPC) and International Convention of Association of Pharmaceutical Teachers of India (APTI).

Life Member of APTI. Area of interest: Novel Drug Delivery System and Clinical Pharmacology.

* Sinhgad Technical Education Society’s, Sinhgad Institute of Pharmaceutical Sciences, 309/310, Off Mumbai-Pune Expressway, Kusgaon (Bk), Lonavala. Dist-Pune. Pin: 410 401. Maharashtra (India).

e-mail: sbb2000@rediffmail.com, shrinivasbumrela@yahoo.co.in

Phone: +91 02114 280076, 280205 Mobile: +919822628406 Fax: +91 02114 280205

Web page: http://in.geocities.com/shrinivasbumrela/shrinivasbumrela.html

2Prof. Kane R. N.

Completed M. Pharm in Medicinal & Pharmaceutical Chemistry from Dept of
Pharmacy, S.G.S.I.T.S. Indore, Rajiv Gandhi Technological University, Bhopal.
Dissertation topic “3-D QSAR Analysis of 2,3 diaryl cyclopentenones as
selective Cyclooxygenase 2 inhibitor”.11 years experience as lecturer
and 3 years experience as Principal. Presently working as Principal at Sinhgad
Institute of Pharmaceutical Sciences, Lonavala.
Various papers are presented in Indian Pharmaceutical Congress (IPC) and International
Convention of Association of Pharmaceutical Teachers of India (APTI). Life Member
of APTI.
Area of Interest: QSAR Studies, NDDS.
Mobile: +91 9890248575 e-mail: rnkane2005@rediffmail.com
.

3Mrs. Dhat Shalaka P.

Completed M. Pharm in Pharmaceutics from Bombay College of Pharmacy, Kalina,
Mumbai in 1997. Have 1 year Industrial and 04 years of academic experience.
Published various papers at International APTI Conference and IJPS. Three papers
accepted for publication in 65th world congress of FIP to be held on 3-8 Sep
2005 in Cairo, Egypt.
Presently working as Lecturer in Pharmaceutics at Sinhgad Technical Education
Society’s Sinhgad Institute of Pharmaceutical Sciences, Lonavala. India.
Area of Interest: Novel Drug Delivery System.
Mobile: 9823270454 e-mail-shalakapd@rediffmail.com

Volumes and Issues: 
Reviews: 

Comments

SAGAR's picture

DEAR SIR

PLEASE GUIDE ME ABOUT HOW TO EVALUATE MCG,METHODS?