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Abstract

Researchers have emphasized the beneficial effects of coffee drinking on blood sugar management in humans. Conversely, the common medication used to treat type 2 diabetes is metformin. The purpose of this study was to investigate potential uses of coffee as an adjuvant to metformin or as a stand-alone treatment for type 2 diabetes Serum HbA levels were considerably lower in groups treated with black coffee (Group 3), metformin (Group 4), and black coffee with metformin (Group 5) than in the 1C diabetic control group (Group 2) (P<0.05).Acceptable salt of metformin, an acid compound or acid salt, an alkaline effervescing compound, one or more compressible binders, and one or more excipients are the components of the effervescent composition of metformin that is the subject of the invention. The weight ratio of the acid compound or acid salt (b) to the alkaline effervescing compound (c) must be greater than 2:1. Tablets and granules made from them are likewise covered by the invention. The invention also pertains to methods for producing effervescent tablets and granules, as well as a method for preparing said composition. The invention specifically targets formulations of metformin hydrochloride as well as the tablets and granules derived from them.

Keywords

Coffee, Metformin, Diabetes gene, Metformin

Introduction

Effervescent tablets offer both qualities of solid and liquid dosage forms. The tablets are administered as a liquid after being distributed and dissolved in water. Although the medicine is presented as a tasty liquid, it nevertheless has the benefits of a solid dosage form, including simple mobility, long stability, and dose precision (Khan et al., 2014; Mohammed et al., 2016). The convenience of use of this dosage type is contributing to its growing popularity. The tablet frequently turns into an effervescent solution when the buoyant delivery mechanism breaks when it comes into touch with water (Agyilirah et al., 1991; Saleh SI et al., 1988). Nonetheless, during production and storage, the dosage forms are subject to numerous crucial factors. Effervescent tablets are susceptible to chemical reactions because of their early effervescent reaction. Many of the components are hygroscopic. Additionally, the presence of a trace amount of water starts a self-propagating reaction that lasts until the product's quality completely deteriorates (Harald, 2003). Accordingly, the preparation processes ought to be conducted in a temperature and humidity-controlled setting (Khan et al., 2014; Josep et al., 2011; Osei-Yeboah et al., 2014).

Machanism of action of caffeine:

Caffeine changed blood glucose maintenance in diabetic males, as evidenced by its ability to raise insulin and serum glycemia levels following an oral glucose tolerance test (OGTT). Insulin sensitivity as measured by insulin sensibility index (ISI) rates decreased. demonstrated the ability of caffeine treatment to regulate catecholamine levels. Long-term caffeine use, however, has been shown to be effective in regulating blood glucose adiponectin levels, which is beneficial for both preventing and treating the release.

Fig. 1 Mechanism of Action of Caffeine

Mechanism of action metformin:

Patients with type 2 diabetes benefit from improved glucose tolerance due to the antihyperglycemic medication metformin, which lowers both basal and postprandial plasma glucose. Its pharmacologic modes of action differ from those of other oral antihyperglycemic drug classes. Metformin enhances insulin sensitivity by boosting peripheral glucose uptake and utilization while reducing intestinal glucose absorption and hepatic glucose synthesis. Metformin does not cause hyperinsulinemia or hypoglycemia, in contrast to sulfonylureas, in either type 2 diabetic patients or healthy individuals (with rare exceptions; see to PRECAUTIONS). Insulin production stays constant throughout metformin therapy, however fasting insulin levels and the daytime plasma insulin response may actually drop.

Foundamental Of Effervescents:

An alkali metal carbonate salt, frequently the API, and a soluble organic acid are the components of effervescence. If water comes into touch with this mixture, carbon dioxide is created.

Common instances of the alkalis and acids that are employed are as follows: Acids such as

  • citric acid,
  • Tartaric acid,
  • Malic acid,
  • Fumaric acid,
  • adipic acid,
  • sodium bicarbonate,
  • carbonate of sodium,
  • sesquicarbonate of sodium,
  • bicarbonate of potassium,
  • carbonate of potassium

Advantage of Effervascent Tablet:

  • You don't have to swallow the tablet.
  • Good intestinal and stomach tolerance.
  • Increased mobility.
  • Better palatability.
  • Better stability.
  • A more reliable reaction.
  • Significant levels of active substances are included.
  • Precise dosage.
  • Enhanced Therapeutic Impact.
  • Effervescent pills may be a viable option in isolated locations, particularly those where parenteral forms are unavailable because of exorbitant costs or a shortage of trained medical personnel.

Effervescent Tablets' Disadvantages:

  • Some of the active substances have an unpleasant taste.
  • Special packaging materials are needed for larger tablets.
  • A significant number of more or less costly excipients and specialized production equipment make it rather costly to produce.
  • Although a fine dispersion is now generally accepted, a clear solution is recommended for administration

METHODS AND MATERIALS:

Metformin HCl effervescent granule preparation:

The preparation of metformin effervescent granules involved a number of changes, including the use of an Ultrasonic Bath (Elmasonic E30H), the addition of PVP K-30, color, and flavor, as well as adjustments to the order and concentration of the excipients used, as detailed by Ashtosh, Rajesh, and Mukesh (Mohapatra et al., 2008). The materials indicated in Table 1 were used to make Metformin Effervescent Granules. Every component, including sodium bicarbonate, citric acid, tartaric acid, aspartame, erythritol, mannitol, metformin, and saccharin Na, was run through sieve number 40. Each formulation's required quantity is listed in Table 1, and all of the ingredients listed above were jointly crushed using a pestle and mortar. Granules were prepared using isopropyl alcohol and PVP K-30 as binder.Using an ultrasonic bath, PVP K-30 and both colors(Sunset Lake and Tartrazine Yellow) were dissolved in isopropyl alcohol in a 2:1 ratio. Both solutions were combined and used to soak the aforementioned dry mixture once the color and PVP K-30 had been thoroughly mixed. After passing through sieve number 60, the wet substance was dried in a Daihan Labtech Co. oven set to no more than 50?C. The desiccated particles wereAfter passing through sieve number 40, the dried granules were combined with orange taste and p

Drug-excipient compatibility study:

The following excipients, which are utilized in the experiments, were examined for this study: These excipients were combined in various ratios based on the functional category. These combinations were maintained at 45°C S and 40°C + 75% RH.No.

Table 1-Category of Excipients

Sr. No.

Excipients

Category

1

Citric acid

Acidifying agent

2

Sodium citrate

Buffering agent

3

Tartaric acid

Acidifying agent

4

Sodium bicarbonate

Alkalizing agent

5

Sodium carbonate

Alkalizing agent

6

Ascorbic acid

Antioxidant

7

Polyethylene glycol-6000

Binding agent

8

Polyvinyl pyrollidone-30

Binding agent

9

Fumaric acid

Intermediate metabolite

10

Acidalant sodium benzoate

Lubricant

11

Sodium lauryl sulphate

Lubricant

12

Mannitol

Binding agent

13

Acesulfum potassium

Sweetner

Pre-compression study

Angle of repose (θ):

This is the greatest angle that can exist between a powder pile's surface and a horizontal plane. The angle of repose can be used to quantify the frictional force in loose powder or granules. It serves as an indicator of the powder's flow characteristics.49–50 tan θ = tan-1 (H/R) θ = H/R The angle of repose is denoted by θ. H is the pile's height. R is the pile's base radius. At a specific height (H), the powder combination was permitted to pass through the funnel that was fastened to a stand. The height and radius of the resulting powder pile were then measured in order to determine the angle of repose. The powder particles were carefully positioned to roll and slip over one another.

through the funnel's sidewalls. Angle of repose and powder flow characteristic are related.

Angle of repose as a measure of the characteristics of powder flow

Table 2: Angle of repose as a measure of the characteristics of powder flow

Repose angle (Degree)

Flow Type

<20

Excellent

20-30

Good

30-40

Acceptable

>40

Very good

Flow Rate:

The rate at which a specific mass emerges from a funnel with an appropriate diameter is known as the flow rate of a powder. Accurately weighed amounts of grains from each formulation were poured into a funnel with an 8 mm diameter opening to ascertain the flow rate. A timer was used to measure the amount of time needed for the entire granule mass to emerge from the aperture. The flow rate was determined using the following formula

Flow rate = weight of granules

                      Time in second

Bulk Density:

The mass of a powder was divided by the bulk volume in cm³ to determine the bulk density. After passing through a conventional sieve number 20, the sample of roughly 50 cm3 of powder was carefully added to a 100 ml graduated cylinder. Three times, the cylinder was dropped from a height of one inch onto a hard wood surface at 2-second intervals. The final volume in cm3 of the sample contained in the cylinder was then divided by the sample weight in grams to determine the bulk density of each formulation. The following equation was used to calculate it:

Df = M/Vp where

Df = stands for bulk density.

M =is the sample weight in grams.

Vp = is the granules' ultimate volumes in cm3.

Tapped density:

The mass of a powder was divided by the tapped volume in centimeters to determine the tap ped density.

A 100 ml graduated cylinder is carefully filled with a sample of roughly 50 cm3 of powder th at has already been run through a standard sieve number 20.

The cylinder was dropped 100 times from a height of 1 inch onto a hard wood surface at 2- second intervals.

The final tapped volume in cm3 of the sample contained in the cylinder was then divided by the sample weight in grams to determine the tapped density of each formulation.

It was computed using the following equation:

Do = M/Vp where

Do= is the bulk density.

M= is the sample weight in grams.

Vp = granules' ultimate volumes in centimeter

Carr's Index:

Carr created an indirect technique for calculating powder flow from bulk densities. The proportion Potential powder arch or bridge strength and stability were directly correlated with a powder's compressibility. Each formulation's Carr's index was determined using the following equation

Where

Df= stands for bulk density, poured bulk, or fluff. Do = Consolidated or Tapped Bulk Density.

Carr's Index as a powder flow indicator:

Table 3: Carr's Index as a powder flow indicator

Carr's index (%)

Flow type

15-15

Outstanding Flow type

12-16

Good

18-21

Passable to fair

23-35

Poor

33-38

Very low income

>40

Very impoverished

Evaluation of Effervasent Tablet:

Weight variation:

To ascertain whether several tablet batches are uniform, weight variation was calculated. 20 pills were weighed separately, the average weight was determined, and the weights of the individual tablets were compared to the average. If no more than two tablets deviate from the percentage restriction and no tablet differs by more than twice the percentage limit, the tablets pass the test. Table No. 6.18 displays the weight variation specification according to I.P. Limit of IP/BP USP

80 mg or less 10% of 130 mg or less Over

80 mg or Not more than 250 mg 7.5% Between 130 and 324 mg

250 mg or more 5% Over 324 mg

Tablet Thickness and Diameter:

For consistency in tablet size, tablet thickness and diameter were crucial. Vernier Calipers were used to measure diameter and thickness.

Tablet Hardness:

The hardness of a tablet determines how resistant it is to breakage or shipment under storage, transportation, and handling conditions prior to use. The Monsanto Hardness Tester was used to measure the hardness of each formulation's tablets. The hardness was expressed in kilograms per centimeter. The force needed to shatter a tablet under diametric compression is known as tablet crushing strength or hardness. For uncoated tablets, a hardness of roughly 3-5 kg/cm2 is deemed adequate, and the force is expressed in kilograms.

Friability (F):

The Roche friabilator was used to determine the tablet's friability. This apparatus rotates a plastic chamber at 25 rpm, dropping a tablet six inches high with each rotation, subjecting it to the combined effects of shock and abrasion. A sample of tablets that had been previously weighed was put in the friabilator and rotated 100 times. The tablets were reweighed after being dusted with a gentle cotton towel. 0.5 to 1% is the USP limit. The formula provides the friability (F)

Effervescence time measurement:

One pill is put in a beaker with 200 milliliters of filtered water at 20 °C ± 1 °C. The effervescence period ends when a clear solution free of particles is achieved. For every formulation, the average of three measurements must be provided.

Effervescent solution determination

As soon as the dissolve time is over, a pH meter is used to measure the pH of the solution using one tablet in 200 milliliters of filtered water at 20 ± 1 °C. For every formulation, repeat the experiment three times.

CO2 content measurement:

Weight changes were calculated following the dissolution of one effervescent tablet in 100 milliliters of a 1N sulfuric acid solution. The amount of CO2 (mg) per tablet is displayed as the weight difference that was obtained. shows the three determinations' averages.

Evaluation of the water content:

For four hours, ten tablets of each formulation are dried in a desiccator filled with activated silica gel. It is okay to have 0.5% or less water.

Content Uniformity:

Ten tablets were chosen at random. After being moved into a 50 mL volumetric flask, each tablet was dissolved and diluted with 50 mL of phosphate buffer (pH 6.8). Phosphate buffer (pH 6.8) was used to dilute one milliliter of this solution to one hundred milliliters. UV spectroscopy at 246 nm was used to measure the amount of medication in each pill. IP is the standard limit for content uniformity:

USP: not more than 25 mg or 25%; BP: not more than 2 mg or 2%;

IP: active less than 10 mg or 10%.

Limit of 10 tabs NMT If two or three individual values are outside the range of 85 to 115%, then one-tab deviates from that range and none is outside of 75 to 125% of the average value/IP/BP/USP (Relative Standard Deviation less than or equal to 6%). Determine the moisture content balance Three desiccators are made with saturated salt solutions of potassium nitrate (to create 90% relative humidity at 18°C), sodium chloride (to create 71% relative humidity at 18°C), and sodium nitrite (to create 60% relative humidity at 18°C). Each formulation's three pills are put in desiccators. The Karl Fischer method and the autotitrator device are then used to calculate the equilibrium moisture content on the first day and seven days later.

Studies on Dissolution:

Using the USP Dissolution Testing Apparatus II (Paddle type), the rate at which atorvastatin was released from mouth-dissolving tablets was ascertained. Nine hundred milliliters of phosphate buffer with a pH of 6.8, kept at 37±0.50C, served as the dissolving media. For the duration of the investigation, the paddle speed was maintained at 50 rpm. Five milliliters of samples were taken out every five minutes, diluted to ten milliliters, and then replaniced with five milliliters of fresh dissolving media kept at the same temperature. The materials were subjected to spectrophotometric analysis at 246 nm with a blank of phosphate buffer pH 6.8. The volume of medicine released and the percentage of drug released at various time intervals were calculated by analyzing the raw dissolution data.

CONCLUSION:

The study investigated the significant correlation between compositions and test parameter results. When compared to regular tablets, effervescent pills improve the absorption of medications and have appealing aesthetic qualities. After a successful bioequivalence study to assess the efficacy of the prepared effervescent tablets, pharmaceutical companies worldwide can adopt this formulation, which will be a more appealing option for diabetic patients, particularly those receiving long-term anti-diabetic therapy. The study found that the most acceptable shelf life for metformin effervescent granules was 510 days at 4?C and 425 days at room temperature. It also found that the granules were most stable when stored at 4?C. Additionally, of the several Effervescent Granule formulations, the EG4 formulation has good flow properties with an angle of repose less than 30 and a quick disintegration in aqueous solution. Granules could therefore be an additional dosing form for antidiabetic medications.

REFERENCES

  1. Gharti KP, Thapa P, Budhathoki U, Bhargava A, Formulation and in vitro evaluation of floating tablets of hydroxypropyl methylcellulose and polyethylene oxide using ranitidine hydrochloride as a model drug, Journal of Young Pharmacists, 2009; 4(4):201-208.
  2. Singh BN, Kim KH, Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention, Journal of Controlled release, 2000; (63):235–59.
  3. Deepali DW, Madhav MS,       Jain DS, Gastroretentive Floating Microspheres: A Review, International Journal of Pharmacy &Technology, 2011; 3(4):1783-1799.
  4. Singh LP, Rajesh KS, Umalkar DG, Chauhan VK, Rana VK, Vasava KS, Floating Effervescent Tablet: A Review, Journal of pharmaceutical and biomedical sciences, 2011; 5(11):1-6.
  5. Agyilirah GA, Green M, DuCret R, Banker GS, Evaluation of the gastric retention properties of a cross-linked polymer coated tablet versus those of a non-disintegrating tablet, International Journal of Pharmaceutics, 1991; 75: 241–47.
  6. Mohrle, R., Liberman, L,Schwartz L, Pharmaceutical Dosage Form, Vol. 1, Marcel Decker Inc., New York, 2005; 285- 292.
  7. Lachman L, Liberman HA, Kanig JL. The theory and practice of industrial pharmacy. 3rd ed. Philadelphia: lea and febiger; 1986.
  8. Swarbrick J, Boylan JC. Encyclopaedia of pharmaceutical technology. New York: Marcel Dekker; 2002
  9. Harald S, Effervescent Dosage, Pharmaceutical Technology Europe, 2003; 15(4): 25–28.
  10. Srinath KR, “Formulation and Evaluation of Effervescent tablets of Paracetamol”,International Journal of Pharmaceutical Research& Development, 2011; 3(3):76- 104
  11. Indian Pharmacopoeia, Government of India Ministry of Health and Family Welfare. Delhi: Controller of Publications 1996; 2: 35, 448, 554.
  12. Howard CA, Lloyd A, Nocholas and Popovich, “Effervescent granules”8th edition“Pharmaceutical Dosage From and Drug Delivery” International Student Edition.- 2000, 172 178.
  13. Dixit N, Maurya SD, Sagar BPS, Sustained release drug delivery system, Indian Journal of Research in Pharmacy and Biotechnology, 2013; 1(3): 305-310.
  14. Shimodaira S, Quality Verification of Dendritic Cell-Based Cancer Vaccine. Pharm Anal Acta, 2016; 7:467.
  15. Hassali MA, Role of Pharmacists in Health Based Non-Governmental Organizations NGO: Prospects and Future Directions, Pharm Anal Acta. 2016; 7:467.
  16. Vergeire DG, Usefulness of Cost Effectiveness: Evidence versus Applicability. Pharm Anal Acta, 2016; 7:456
  17. Indian Pharmacopoeia, Government of India Ministry of Health and Family Welfare. Delhi: Controller of Publications1996; 2: 35, 448, 554.
  18. Howard CA, Lloyd A, Nocholas and Popovich, “Effervescent granules”8th edition“Pharmaceutical Dosage From and Drug Delivery” International Student Edition.- 2000, 172-178.
  19. Dixit N, Maurya SD, Sagar BPS, Sustained release drug delivery system, Indian Journal of Research in Pharmacy and Biotechnology, 2013; 1(3): 305-310.
  20. Shimodaira S, Quality Verification of Dendritic Cell-Based Cancer Vaccine. Pharm Anal Acta, 2016; 7:467.
  21. Hassali MA, Role of Pharmacists in Health Based Non-Governmental Organizations NGO: Prospects and Future Directions, Pharm Anal Acta. 2016; 7:467.
  22. Vergeire DG, Usefulness of Cost Effectiveness: Evidence versus Applicability. Pharm Anal Acta, 2016; 7:456
  23. Abdelmoneim, A. S., Hasenbank, S. E., & Seubert, J. M. (2012). Variations in tissue selectivity amongst insulin secretagogues: A systematic review. Diab ObesMetab, 14(2), 130-138. https://doi.org/10.1111/j.1463 1326.2011.01496.x
  24. Agrawal, A. G., Kumar, A., & Gide P. S. (2015). Self-emulsifying drug delivery system for enhanced solubility and dissolution of Glipizide. Colloid Surf B, 126, 553-560. https://doi.org/10.1016/j.colsurfb.2014.11.022
  25. Agyilirah, G. A., Green, M., & Banker, G. S. (1991). Evaluation of the gastric retention properties of a cross-linked polymer-coated tablet versus those of a non-disintegrating tablet. International Journal of Pharmaceutics, 75(2-3), 241-247. https://doi.org/10.1016/0378- 5173(91)90198-W
  26. Al-Hashemi, H. M. B., & Al-Amoudi, O. S. B. (2018). A review on the angle of repose of granular materials. Powder Technology, 330, 397-417. https://doi.org/10.1016/j.powtec.2018.02.003
  27. Ashish, P., Mishra, P., Main, P., Harsoliya, M., & Agrawal, S. (2011). A review on-recent advancement in the development of rapid disintegrating tablet. Int J Life Sci Pharm Res, 1, 7-16. Effervescent
  28. Aslani, A., & Fattahi, F. (2013). Formulation, characterization, and physicochemical evaluation of potassium citrate tablets. https://doi.org/10.5681/apb.2013.03617 29. Alexandar S and Thyangarajapuram N (2003). Formulation and accelerated stability studies for amiodarone hydrochloride. IJPC, 3: 34-36.
  29. Anthony C Moffat (2004). Clarke’s analysis of drugs and poisons: In pharmaceuticals, body fluids and postmortem material l, 3rd ed; Volume 2, Chicago Pharmaceutical Press, London, pp.1229-1230. 31.Bailey CJ and Day C (2004). Metformin: Its botanical background. Practical Diabetes International, 21(3): 115-117.
  30. Bhusan SY, Sambhaji SP, Anant RP and Kakasaheb RM (2000). New drug delivery system for elderly. Indian Drugs, 37: 312-318.
  31. David B Troy (2000). Remington: The Science and practice of pharmacy, 20th ed; Williams and Wilkins, Lipponcott, Philadelphia, PA, pp.1017-1021.
  32. Hausler, Franz, Rohrich, Till (2007). Effervescent metformin composition and tablets and granules made therefrom, PatientScope.wipo,wo/038979.
  33. Reis CE, Dórea JG, da Costa TH. Effects of coffee consumption on glucose metabolism: a systematic review of clinical trials. J Tradit Complement Med. 2019; 9(3): 184-191.
  34. Butt MS, Sultan MT. Coffee and its consumption: benefits and risks. Crit Rev Food Sci Nutr. 2011; 51(4): 363-373.
  35. Shahid M, Kim M, Yeon A, Andres AM, You S, Kim J. Quantitative proteomic analysis reveals caffeine-perturbed proteomic profiles in normal bladder epithelial cells. Proteomics. 2018; 18(20): 1-20.
  36. Peerapen P, Chanthick C, Thongboonkerd V. Quantitative proteomics reveals common and unique molecular mechanisms underlying beneficial effects of caffeine and trigonelline on human hepatocytes. Biomed Pharmacother. 2023; 158: 1-13.

Reference

  1. Gharti KP, Thapa P, Budhathoki U, Bhargava A, Formulation and in vitro evaluation of floating tablets of hydroxypropyl methylcellulose and polyethylene oxide using ranitidine hydrochloride as a model drug, Journal of Young Pharmacists, 2009; 4(4):201-208.
  2. Singh BN, Kim KH, Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention, Journal of Controlled release, 2000; (63):235–59.
  3. Deepali DW, Madhav MS,       Jain DS, Gastroretentive Floating Microspheres: A Review, International Journal of Pharmacy &Technology, 2011; 3(4):1783-1799.
  4. Singh LP, Rajesh KS, Umalkar DG, Chauhan VK, Rana VK, Vasava KS, Floating Effervescent Tablet: A Review, Journal of pharmaceutical and biomedical sciences, 2011; 5(11):1-6.
  5. Agyilirah GA, Green M, DuCret R, Banker GS, Evaluation of the gastric retention properties of a cross-linked polymer coated tablet versus those of a non-disintegrating tablet, International Journal of Pharmaceutics, 1991; 75: 241–47.
  6. Mohrle, R., Liberman, L,Schwartz L, Pharmaceutical Dosage Form, Vol. 1, Marcel Decker Inc., New York, 2005; 285- 292.
  7. Lachman L, Liberman HA, Kanig JL. The theory and practice of industrial pharmacy. 3rd ed. Philadelphia: lea and febiger; 1986.
  8. Swarbrick J, Boylan JC. Encyclopaedia of pharmaceutical technology. New York: Marcel Dekker; 2002
  9. Harald S, Effervescent Dosage, Pharmaceutical Technology Europe, 2003; 15(4): 25–28.
  10. Srinath KR, “Formulation and Evaluation of Effervescent tablets of Paracetamol”,International Journal of Pharmaceutical Research& Development, 2011; 3(3):76- 104
  11. Indian Pharmacopoeia, Government of India Ministry of Health and Family Welfare. Delhi: Controller of Publications 1996; 2: 35, 448, 554.
  12. Howard CA, Lloyd A, Nocholas and Popovich, “Effervescent granules”8th edition“Pharmaceutical Dosage From and Drug Delivery” International Student Edition.- 2000, 172 178.
  13. Dixit N, Maurya SD, Sagar BPS, Sustained release drug delivery system, Indian Journal of Research in Pharmacy and Biotechnology, 2013; 1(3): 305-310.
  14. Shimodaira S, Quality Verification of Dendritic Cell-Based Cancer Vaccine. Pharm Anal Acta, 2016; 7:467.
  15. Hassali MA, Role of Pharmacists in Health Based Non-Governmental Organizations NGO: Prospects and Future Directions, Pharm Anal Acta. 2016; 7:467.
  16. Vergeire DG, Usefulness of Cost Effectiveness: Evidence versus Applicability. Pharm Anal Acta, 2016; 7:456
  17. Indian Pharmacopoeia, Government of India Ministry of Health and Family Welfare. Delhi: Controller of Publications1996; 2: 35, 448, 554.
  18. Howard CA, Lloyd A, Nocholas and Popovich, “Effervescent granules”8th edition“Pharmaceutical Dosage From and Drug Delivery” International Student Edition.- 2000, 172-178.
  19. Dixit N, Maurya SD, Sagar BPS, Sustained release drug delivery system, Indian Journal of Research in Pharmacy and Biotechnology, 2013; 1(3): 305-310.
  20. Shimodaira S, Quality Verification of Dendritic Cell-Based Cancer Vaccine. Pharm Anal Acta, 2016; 7:467.
  21. Hassali MA, Role of Pharmacists in Health Based Non-Governmental Organizations NGO: Prospects and Future Directions, Pharm Anal Acta. 2016; 7:467.
  22. Vergeire DG, Usefulness of Cost Effectiveness: Evidence versus Applicability. Pharm Anal Acta, 2016; 7:456
  23. Abdelmoneim, A. S., Hasenbank, S. E., & Seubert, J. M. (2012). Variations in tissue selectivity amongst insulin secretagogues: A systematic review. Diab ObesMetab, 14(2), 130-138. https://doi.org/10.1111/j.1463 1326.2011.01496.x
  24. Agrawal, A. G., Kumar, A., & Gide P. S. (2015). Self-emulsifying drug delivery system for enhanced solubility and dissolution of Glipizide. Colloid Surf B, 126, 553-560. https://doi.org/10.1016/j.colsurfb.2014.11.022
  25. Agyilirah, G. A., Green, M., & Banker, G. S. (1991). Evaluation of the gastric retention properties of a cross-linked polymer-coated tablet versus those of a non-disintegrating tablet. International Journal of Pharmaceutics, 75(2-3), 241-247. https://doi.org/10.1016/0378- 5173(91)90198-W
  26. Al-Hashemi, H. M. B., & Al-Amoudi, O. S. B. (2018). A review on the angle of repose of granular materials. Powder Technology, 330, 397-417. https://doi.org/10.1016/j.powtec.2018.02.003
  27. Ashish, P., Mishra, P., Main, P., Harsoliya, M., & Agrawal, S. (2011). A review on-recent advancement in the development of rapid disintegrating tablet. Int J Life Sci Pharm Res, 1, 7-16. Effervescent
  28. Aslani, A., & Fattahi, F. (2013). Formulation, characterization, and physicochemical evaluation of potassium citrate tablets. https://doi.org/10.5681/apb.2013.03617 29. Alexandar S and Thyangarajapuram N (2003). Formulation and accelerated stability studies for amiodarone hydrochloride. IJPC, 3: 34-36.
  29. Anthony C Moffat (2004). Clarke’s analysis of drugs and poisons: In pharmaceuticals, body fluids and postmortem material l, 3rd ed; Volume 2, Chicago Pharmaceutical Press, London, pp.1229-1230. 31.Bailey CJ and Day C (2004). Metformin: Its botanical background. Practical Diabetes International, 21(3): 115-117.
  30. Bhusan SY, Sambhaji SP, Anant RP and Kakasaheb RM (2000). New drug delivery system for elderly. Indian Drugs, 37: 312-318.
  31. David B Troy (2000). Remington: The Science and practice of pharmacy, 20th ed; Williams and Wilkins, Lipponcott, Philadelphia, PA, pp.1017-1021.
  32. Hausler, Franz, Rohrich, Till (2007). Effervescent metformin composition and tablets and granules made therefrom, PatientScope.wipo,wo/038979.
  33. Reis CE, Dórea JG, da Costa TH. Effects of coffee consumption on glucose metabolism: a systematic review of clinical trials. J Tradit Complement Med. 2019; 9(3): 184-191.
  34. Butt MS, Sultan MT. Coffee and its consumption: benefits and risks. Crit Rev Food Sci Nutr. 2011; 51(4): 363-373.
  35. Shahid M, Kim M, Yeon A, Andres AM, You S, Kim J. Quantitative proteomic analysis reveals caffeine-perturbed proteomic profiles in normal bladder epithelial cells. Proteomics. 2018; 18(20): 1-20.
  36. Peerapen P, Chanthick C, Thongboonkerd V. Quantitative proteomics reveals common and unique molecular mechanisms underlying beneficial effects of caffeine and trigonelline on human hepatocytes. Biomed Pharmacother. 2023; 158: 1-13.

Photo
Leena Chavan
Corresponding author

Samarth Institute of Pharmacy, Belhe, Pune 412410, Maharashtra, India

Photo
Ganesh Lamkhade
Co-author

Samarth Institute of Pharmacy, Belhe, Pune 412410, Maharashtra, India

Photo
Pooja Ghule
Co-author

Samarth Institute of Pharmacy, Belhe, Pune 412410, Maharashtra, India

Photo
Rushikesh Raut
Co-author

Samarth Institute of Pharmacy, Belhe, Pune 412410, Maharashtra, India

Leena Chavan*, Ganesh Lamkhade, Pooja Ghule, Rushikesh Raut, Evalution and Development of Antidiabetic Effervescent Tablet of Caffeine, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 3, 855-863. https://doi.org/10.5281/zenodo.15005457

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