1,3,4Department of Pharmaceutics, Konkan Gyanpeeth Rahul Dharkar College of Pharmacy and Research Institute, Karjat, Maharashtra, India.
2Department of Pharmaceutics, Dr. L. H. Hiranandani College of Pharmacy, Ulhasnagar, Maharashtra, India.
Oral dosage forms are the most often used method of administering medication, they have certain drawbacks, such as a slower rate of absorption. By consuming liquid dose forms, this can be avoided. The majority of APIs, however, have been discovered to be unstable in liquid formulation. An alternate approach to creating a dosage form that can accelerate the dispersion and degradation of medications is the effervescent technique. Because of their quick onset of action and ease of administration, effervescent tablets are growing in popularity. Usually, they comprise acidic substances and carbonates or bicarbonates that react rapidly with water to release carbon dioxide, enhance API solubility, and hide flavor. The benefits and drawbacks of effervescent tablets, effervescent reactions, active ingredients that can be formulated, Effervescent Dosage Form Manufacturing, Effervescent system for Geriatric and Paediatric Population, Process, Formulation methods, Raw material, tablet evaluation and Release kinetic modeling of effervescent tablets are all covered in this article.
Despite drawbacks including slow absorption, which prolongs the beginning of effect, oral dosage forms remain the most widely used method of medication delivery. This will be resolved by administering the medication in liquid form; however, the stability of many APIs in liquid form is limited. Therefore, effervescent tablets serve as a substitute dosage form. Typically, three to four ounces of water are used to dissolve one dose of an effervescent tablet. Since effervescent products have been pre-dissolved in a buffer solution, they do not come into direct contact with the gastrointestinal tract. The stomach and intestines can take it well because of the decreased gastrointestinal inflammation. The tablet is dissolved in a glass of water just before administration, and the pharmaceutical solution or dispersion that results should be consumed immediately. Because tartaric and citric acids react with alkali metal carbonates or bicarbonates when water is present, internal forces cause the tablet to break apart rapidly. [1] The emission of CO2 gas improves both the flavour masking effect and the breakdown of API in water. The advantages of effervescent tablets over other oral dosage forms include the formulator's ability to maximize flavor, a softer impact on the user's stomach, as well as marketing considerations. These tablets are made by either heat fusion or wet fusion. The pills are soft enough to have a fast enough effervescent reaction to compress. To prevent the development of insoluble scum on the water's surface, water-soluble lubricants are utilized. Since sucrose is hygroscopic and adds excessive bulk to the pill, saccharin is employed to provide sugar to the formulation. Processing is done under carefully regulated climate conditions to avoid an effervescent response. The packing is below 25% relative humidity at 25ºC. Moisture from the environment and user hands can potentially cause product loss consistency following jar opening. The most popular effervescent tablet on the market right now is aspirin. When gas escapes from an aqueous solution, it causes effervescence, which is characterized by foaming or fizzing. Soft drinks and other carbonated liquids are frequently used as examples. The development of gas bubbles from a liquid as a result of a chemical reaction is known as effervescence. Since water is one of the reaction products, it speeds up the rate of the reaction and makes it more difficult to stop, even when there is only a little amount of water present as a catalytic agent. Because of this, the entire process of producing and storing effervescent items is designed to minimize interaction with water. Both the flavor masking effect and the breakdown of API in water are enhanced by the CO2 gas emission. [2]
Figure: Mechanism of Effervescence. [2]
According to USFDA, effervescent tablets are intended to dissolved or dispersed in water before administration. When acid and bicarbonates react with water, effervescent tablets release carbon dioxide. The most often utilized acids are fumaric, tartaric, citric, and adipic acids. Both potassium and sodium bicarbonate are utilized as bicarbonates. Polyvinylpyrrolidone serves as a binder in these tablets. [3]
2.Benefits of effervescent tablets over regular tablets
Good taste Since effervescent tablets dissolve in liquids like water or fruit juice, they are popular since they frequently taste better than ordinary tablets. Effervescent tablets dissolve quickly, allowing you to benefit fully from the substances, while regular tablets dissolve slowly, which may result in lower absorption rates.
Good Distribution Ordinary tablets might be slightly distributed and dissolve slowly in the stomach if they are imported, which may lead to irritation. An effervescent tablet's benefit is that all of the components dissolve uniformly, preventing substance accumulation. In addition to the greatest taste, this also means a lower risk of irritation and more effective ways to include components.
Alternative to Regular They are regarded as an excellent alternative for people who might have difficulty swallowing because of age or disease. Effervescent tablets can be much easier for elderly persons who occasionally struggle with swallowing but must take medication or vitamins on a regular basis. Additionally, they might be a great substitute to normal tablets for people who have sore throats or other medical conditions that make swallowing difficult.
Fast onset of action The primary benefit of effervescent tablets is that the medication is already in solution when they are taken. As a result, absorption occurs earlier and is more efficient than a regular tablet. The pH of the effervescent medication is just right for absorption when it is delivered to the stomach.
No need to Swallow Tablet Because they are liquid, effervescent tablets are convenient to take. The number of people who dislike ingesting tablets and capsules or who are unable to take them is increasing. One dose can often be transported in just three or four ounces of water using an effervescent dosage form.
Good stomach and Intestinal Tolerance In a buffered solution, the effervescent tablet entirely dissolves. There is less irritation and more tolerance when there is less localized touch in the upper stomach. Additionally, buffering keeps intestinal acids from reacting with the drug, which can be a major factor in stomach tolerance. [4]
Increased fluid intake: Effervescent tablets offer both the extra fluid intake and the targeted therapeutic benefit. Effervescent table water helps with regular fluid intake in cases of diarrhoea and hot summer temperatures.
Best compatibility: A buffer consisting of a balanced ratio of carbonates and acids is present in the effervescent tablet. It has great compatibility with the stomach. [5]
3.Drawbacks of effervescent tablet
Bulk Size: Effervescent tablets are often larger as they include effervescent ingredients. Special packaging materials are needed for this increased volume.
Taste Considerations. Patient compliance may be impacted by effervescent tablets' inability to adequately mask this unpleasant taste.
Cost: Higher production costs can result from the expensive excipients used in effervescent tablets.
Special Production Facilities: Effervescent tablet manufacturing calls for specialized facilities, which can make the process more complicated and expensive. [6]
4.Effervescent reaction
C6H8O7 (aq) + 3NaHCO3 (aq) → Na3C6H5O7 (aq) + 4H2O + 3CO2 (g) ↑
Citric acid + Sodium bicarbonate → Sodium citrate + Water + Carbon dioxide
Even a small amount of water can act as a catalytic agent in this reaction, and as water is one of the reaction products, it speeds up the rate of reaction and makes it more difficult stop. [7]
5.Active ingredients that can be formulated in effervescent tablets
· Drugs that call for a high dose Over 2 g of water-based active components are included in a single dose of a typical effervescent tablet, which has a diameter of approximately 1 inch and weighs 5 g. It can be administered as a powder if a higher dosage is required. E.g., N-acetyl cysteine effervescent tablets. [8]
· Drugs that are challenging to digest or have stomach disturbances: A good example would be calcium carbonate tablets, which are the most common form of calcium. In a normal tablet or powder, the calcium salt of carbonate dissolves in the stomach's acidic pH before being carried into the digestive tract for absorption. However, CO2 is released as calcium carbonate dissolves in the digestive tract, usually causing gas in the stomach. However, a calcium carbonate tablet may pass through the stomach undissolved as people age because their stomach acid lowers. That could lead to constipation. But when calcium is given as an effervescent formulation, it dissolves in water and is readily absorbed by the body.
• Drugs that are sensitive to pH, such as amino acids and antibiotics The low pH of the stomach might cause active ingredients to become denatured, lose their effectiveness, or stay inactive. However, by buffering the water-active solution, effervescent substances can stop it from breaking down or inactivating, causing the stomach's pH to become less acidic and more alkaline. The buffering effect of carbonation causes the stomach to empty rapidly, usually within 20 minutes into the small intestine, resulting in optimal absorption of the active ingredient.
· Those who are sensitive to oxygen, dampness, or light. Effervescent treatments frequently include less than 0.5% free moisture. Aluminium that is 0.001 inches thick should be the main component of the package formulation. For the contents to be preserved and any environmental harm to be avoided, it must be able to totally block light, oxygen, and moisture. [9]
6.Effervescent Dosage Form Manufacturing.
As raw materials are hygroscopic, it is essential to maintain strict environmental conditions throughout the manufacturing of effervescent products in order to guarantee product stability and avoid early responses. To prevent sticking and moisture absorption, it is important to keep the relative humidity (RH) below 20% at 21°C or 25% at 25°C. While open systems need regulated ventilation to maintain low moisture levels, closed handling solutions—such as the use of intermediate bulk containers and specialized blenders—help reduce exposure. The quality of granules and tablets is greatly impacted by the granulation process, which is usually carried out in batch mode. High compression forces, careful lubrication, and occasionally pre-compression are required because to issues including the low compressibility of effervescent components and the restricted space for compression-enhancing excipients. Long-term stability is mostly dependent on packaging, which can include aluminium foil wraps, hermetically sealed containers, or tubes with silica gel tops to regulate moisture. For a product to remain stable over its shelf life, proper handling and packaging are crucial. [10]
7.Effervescent system for Geriatric and Paediatric Population
Geriatric population:
Swallowing problems: Age-related illnesses or adverse drug reactions frequently cause the elderly population to suffer from dysphagia, or difficulty swallowing. By turning solid dose forms into liquid form, effervescent formulations can offer a solution, lowering the danger of choking and simplifying the intake of medications for senior citizens.
Avoiding bitter tastes: Elderly people may also be more susceptible to the bitter flavor of some drugs. To improve palatability and medicine acceptance among older adults, effervescent systems can be used to mix pharmaceuticals with tastes and sweets.
Hydration promotion: Before being consumed, effervescent formulations usually need to be diluted in water. In addition to providing the required drugs, this encourages older adults—who may be more susceptible to dehydration—to drink enough fluids. [10]
Paediatric Population:
Swallowing ease: Since children, especially young ones, frequently have trouble swallowing tablets or capsules, effervescent formulations offer a convenient substitute because they dissolve quickly in water, producing a pleasant-tasting effervescent solution that is easier for kids to consume.
Taste masking: Since many pediatric medications have a bitter taste, which makes administering them difficult, effervescent systems can add Flavors and sweeteners to the formulation, effectively masking the bitter taste and making the medication more palatable for kids.
Enhancement of medication compliance: Children are more likely to take their medication voluntarily when it is more pleasurable and doesn't cause discomfort during administration. [11]
8.Process
The following phases essentially comprise the entire production process of effervescent formulation:
• Dosing of the ingredients
• Mixing/Granulation
• Lubricating
• Tableting
•Packaging
Effervescent formulations are often manufactured using a semi-continuous process. The crucial processes that have a significant impact on the creation of the final formulation are granulation, acid-base mixing, and pre-drying. Granule lubrication and compression must be done correctly to get the required level of effervescence. [12]
The effervescent formulation comprises a minimum of one medication, whose physiochemical parameters are divided into three stages: pre-drying and drying stage.
The following are the stages of variation:
• The humidification of the effervescent mixture;
• The humidification mixture's pre-drying;
• The granulation mixture's final drying. [13]
Figure: Manufacturing flow chart of Effervescent Formulation [13]
9.Formulation methods
Wet granulation
Wet granulation is the most popular agglomeration method. Wet massing of a powder blend with a granulating liquid, wet sizing, and drying are the only steps in the wet granulation process.
Wet granulation involves several crucial processes.
1. mixing excipients and drug
2. Preparing the binder solution
3. Combining the powder mixture and binder solution to create a wet mass
4. Moist granules drying
5. Combining lubricant, glidant, and disintegrant with screened granules.
Advantage:
Disadvantage:
1. Because it requires labor, time, equipment, energy, and space, it is an expensive procedure.
2. Additional material loss at different manufacturing phases. [14]
Dry granulation:
The powder mixture is compacted in the dry granulation process without the use of heat or solvent. Of all the granulation techniques, it is the least preferred. The two fundamental processes are compressing the material into a compact and then milling the compact to create granules. There are two techniques for dry granulation. Slugging is a more popular technique that involves recompressing the powder and milling the resulting tablet or slug to produce the granules. The alternative is to use a machine like a chilosonator to recompress the powder using pressure rolls. [15]
Roller compaction
Using a pressure roll, a device called a chilsonator can be utilized for compression. In contrast to a tablet, a chilsonator combines weight and constant flow device. The powder is fed between the rollers from the hopper, which features a powder compaction area fed by a spiral auger. Like slugs, aggregates are filtered to form granules. [16]
Direct compression
For the manufacturing of effervescent tablets containing acetylsalicylic acid, direct compression has proven to be a successful substitute for dry granulation. Problems with process efficiency and operational stability can be resolved with this process. Because this technology can only be used in the greatest production circumstances, its practical applications are limited. This is due to the need for complex combinations of non-dissolving, compressible, and free-flowing basic ingredients. [17]
10.Advancement in granulation:
Steam granulation:
Wet granulation has been modified. In this case, steam is utilized as a binding agent rather than water. High uniform distribution and high distribution rate into powders are two of its many advantages. In comparison to the use of organic solvent vapor water, the steam granules are rounded on top, have a large surface area that increases the drug's dissolution rate from gramiles, and have a good favorable heat balance during the drying step. This results in a smaller processing time and a higher number of tablets produced per set. Additionally, the steam is sterile and free of contamination, so the total value can be kept under control. It is possible to manufacture flavor granules with low dissolving rates without affecting the availability of the medicine. [18]
High shear granulator
This is the most often utilized arrangement for pharmaceutical granule assembly on an industrial basis. Once more, this method enables complete integration with both upstream and downstream machinery, and it even incorporates a wet mill in between the dryer and granulator. It is simple to load, mix, and granulate a second batch in the high shear granulator while drying the first batch in the fluid bed prior to discharge thanks to contemporary control systems. In situ cleaning of all equipment is possible with a single automated procedure. [19]
Fluidized-Bed Granulation
In fluid bed granulation (also called agglomeration), particles are suspended in an air stream and a liquid is sprayed from the top of the system down onto the fluidized bed (top-down spray). The particles in the spray's path become slightly wet and sticky, and when they collide with other particles in the material bed, they stick to them to form granules. [20]
Figure: Fluidized-Bed Granulator [4]
Hot melt granulation
In a melt granulation process, a meltable binder is used in place of the binder solution used in a typical wet granulation process. Although this binder can be added molten, the high shear procedure has the benefit of enabling the addition of the binder in its solid condition. The energy contributed by the mixer's friction and, consequently, the bowl's heated jacket causes melting. [21]
11.Raw materials
1.Acid Sources: Food acids, acid anhydrides, and acid salts are the three primary sources of the acidity required for the effervescent process.
Food Acids
Acid anhydrides
As acid anhydrides hydrolyze into acids that combine with carbonates to release CO?, they can improve effervescent products. Succinic anhydride, a desiccant used in denture soaks, reduces caking.
Acid salts
Acid salts like sodium dihydrogen phosphate, sodium acid pyrophosphate, and acid citrate salts are water-soluble and form mildly acidic solutions, making them suitable for effervescent products. While safe for ingestion, they help in generating CO?. In contrast, sodium bisulfite is a strong reducing agent not safe for consumption, used in non-edible cleaners like toilet tablets.
2. Carbonate compounds: are key in generating carbon dioxide in effervescent tablets, with bicarbonates being more reactive and commonly preferred.
3.Binders and Granulating: Agent Binders are used sparingly in effervescent tablets as they delay tablet breakdown. Dry binders like lactose, dextrose, and mannitol are commonly used. Isopropanol and ethanol don’t act as binders but are used to dissolve binders like PVP. Water functions both as a binder and a solvent.
4.Lubricant: While making effervescent tablets on high-speed machinery, lubricants are essential. Although insoluble and effective, stearates (zinc, calcium, and magnesium) may slow disintegration. PEG 8000 and sodium benzoate both dissolve in water and aid in breakdown. Lubrication is aided by oils, PTFE, and talc. Magnesium lauryl sulfate is milder than sodium lauryl sulfate, which is effective but may prevent breakdown if used excessively. A combination of PEG and magnesium lauryl sulfate provides superior tablet performance and solubility.
5.Diluents: Diluents are rarely needed in effervescent tablets due to the bulk of active ingredients. However, sodium chloride and sodium sulfate can be used to increase tablet density when needed.
6.Other Ingredient:
1.oxidizing agents - sodium per-borate or potassium monopersulfate
2.Sweeteners: Acesulfame potassium, Sodium saccharin, Aspartame, Sucralose
3.Flavours: Powdarome Lemon, Powdarome Orange, Strawberry Flavour, Tutti Frutti Flavour [22] [23]
12.Evaluation tests of effervescent granules
1.Angle of repose (θ)
At a specific height (h), the dry mixture powders were allowed to pass through the immovable funnel to a stand. The height and radius of the resulting pile of powders were then measured in order to determine the angle of repose.
Tan ? = h / r.
? = tan-1 (h / r)
where h and r were the powder heap's height and radius, respectively, and θ was the angle of repose. Excellent flow is indicated by an angle of repose value less than 250, whereas poor flow is indicated by an angle larger than 400. [24]
2.Bulk density
By pouring the presieved drug excipient mixture into a graduated cylinder, the apparent bulk density was determined, and the volume and weight were measured "as it is." It is described in g/ml and is specified by
Db = M / V0
where V0 is the powder's bulk volume and M is its mass.
3.Tapped density
It is calculated by dividing the granules' weight by their tapped volume.
Dt = M / Vt
where Vt is the powder's tapped volume and M is its mass. (Tambe*, 2021)
4.Carr’s compressibility index
Carr has created a way to measure powder flow indirectly using bulk densities. A powder's potential strength and stability for an arch or bridge could be directly determined by its % compressibility.
Compressibility index = Tapped density – Bulk density
Tapped density [26]
5.Hausner's ratio
The following equation is used to compute Hausner's ratio. A Hausner's ratio below 1.25 indicates better flowing characteristics than one that is greater. Hausner's ratios, which range from 1.25 to 1.6, indicate qualities of moderate flow. When Hausner's ratio exceeds 1.6, more cohesive particles will be visible.
Hausner ′ratio = tapped density
bulk density [27]
13.Evaluation tests of effervescent tablets
Determination of Effervescent Solution pH
After the dissolution period, dissolve one effervescent tablet in 100 mL of water at 25 °C. to use a pH meter digital tester to measure the pH solution. [28]
Water Content
Ten tablets were placed in a desiccator with silica gel and dried for four hours. The water content percentage was computed as follows.
|
× 100 |
Tablet weight before drying – tablet weight after drying Tablet weight before drying [29]
Tablet dissolving time
The amount of time needed for a tablet to dissolve completely in 200 ml of water at room temperature was used to calculate the dissolving time. [30]
Tablet Thickness Measurement
Each formulation's tablet thickness was measured using calibrated Vernier calipers. Variations in average thickness shouldn't deviate from their limitations by more than 5%. [31]
Uniformity of content:
Check to see if the active ingredients in 10 units of a single-dose formulation are equal. The composition of each unit should be between 85 and 115% of the mean. The test is considered faulty if one or more units fall outside of this range or the 75–125% range. Test 20 more units if one unit is between 75 and 125% but not within the 85–115% range. The test is deemed good if none of the 30 total units fall outside of the 85–115% range, and no units fall outside of the 75–125% range. [32]
Weight variation
A weight variation test was used to evaluate dose unit uniformity. From each batch, twenty tablets were selected at random, weighed, and their weights were compared to the calculated mean weight. [33]
In-vitro disintegration time
The process by which a tablet fragments into smaller pieces is called disintegration. The in vitro disintegration period of a tablet was ascertained using a standardized disintegration test, which was recently applied to rapid disintegration agents.
METHODS:
The disintegration took place in a beaker with 200 ml of media. The medium was water at a temperature of 15 to 25°C. A single tablet was inspected at a time, and it was considered to have dissolved when the fragments were equally spaced. [34]
Amount of carbon dioxide content
Three tablets are placed in three beakers with 100 mL of a 1 N sulfuric acid solution. The weight difference before and after tablet dissolution was used to calculate the amount of CO2 emitted (mg). [35]
Hardness
Monsanto Hardness Tester's determination of hardness. (Tambe*, 2021)
Friability
After calculating total weight, twenty randomly selected tablets were placed in the friabilator chamber for four minutes at 25 rpm in order to conduct the friability test. Tablets with a weight loss of less than 1% passed the friability test. Percentage friability: Initial weight – Final weight/ Initial weight x 100 (Tambe*, 2021) [36]
In vitro dissolution study
In an effervescent tablet dissolution test, a tablet is immersed in a certain amount of water at a specified temperature using a dissolution device. As the paddle or basket of the apparatus rotates to produce agitation, the drug concentration in the water is periodically measured using a spectrophotometer or a comparable technique. The test is administered three times, and the results are compared to the relevant efficacy and quality criteria. [9]
14.Release kinetic modeling of effervescent tablets [37] [38] [39] [40] [41] [42]
Drug release from pharmaceutical dosage forms has been the focus of considerable and profitable scientific research in recent years. Every time a new dosage form is created, it is important to make sure that the drug releases through the proper channel. The use of mathematical formulas that express the release outcomes as a function of certain of the dosage form features facilitates the quantitative examination of the values acquired in release testing. These mathematical models can occasionally be obtained by theoretically analyzing the process that is taking place. Kinetic models with a dissolved drug amount (Q) as a function of test time (t) or Q=f (t) have been used to characterize drug dissolution from dosage forms. There are several widely used analytical definitions of the Q (t) function, including zero order, first order, Higuchi, and Korsmeyer–Papas. It has been acknowledged that in-vitro dissolution is a significant pharmaceutical dosage form that can affect the release aspect in the creation of new drugs. It can be employed as a stand-in for the evaluation of bioequivalence under specific circumstances. Drug dissolution from immediate and modified release dose forms is described by a number of theories and kinetics models. The drug dissolution profiles are represented by a number of models in which the amount of medication dissolved from the pharmaceutical dosing system is ft, which is a function of t (time). Generally speaking, there is no theoretical foundation for tablets, capsules, coated forms, or prolonged release forms; occasionally, more suitable empirical formulae are employed. The primary release mechanism for a water-soluble drug integrated into a matrix is diffusion, whereas the primary release mechanism for a low water-soluble drug is matrix self-erosion. In contrast to their differential profiles, the cumulative profiles of the dissolved medication are more frequently used to carry out these investigations. Statistical analysis and model independent techniques can be utilized to compare the dissolution profiles of two medicinal products that are model dependent [curve fitting]
Zero order kinetics
The following equation can be used to illustrate medication dissolution from dosage forms that do not disintegrate and release the drug gradually.
Wo-Wt= Kt
where K is the proportionality constant, Wo is the initial amount of drug in the dosage form, Wt is the initial amount of drug in the dosage form at time(t), Simplifying and dividing this equation
Ft=Kot
where ft = 1-(Wt-Wo) and Ko is the zero order of release constant, and ft is the fraction of drug dissolved in time t.
The modified release dosage form can be described using this relation; this model can be simply expressed using the following relation.
Qt = Qo + Kot
where Qt is the drug's dissolution time (t). The amount of drug in the solution is denoted by Qo.
First order kinetics
The use of this The model for drug dissolution investigations was first suggested by Gibaldi and Feldman in 1967, and Wagner followed suit in 1969. The Noyes-Whitney equation shows that a surface action is implied by the dissolving phenomenon of solid particles in a liquid medium.
DC/dt= K (Cs-C)
where Cs is the solubility in the equilibrium at the expression temperature and C is the solute's concentration at time t. The first order proportionality is denoted by K.
Higuchi model
In order to investigate the release of water-soluble and low-soluble drops integrated into the matrixes, Higuchi created a number of theoretical models. The following relationship was found when the drug particles were distributed in a homogeneous matrix acting as diffusion media:
ft = Q= D(2C-Cs) Cst
where D is the drug molecules' diffusivity (diffusion constant in matrix), C is the drug's starting concentration, Cs is its solubility in the matrix media, and Q is the amount of drug released in time t, per unit area.
dQ = Cdh – ½ (Csdh)
but, in accordance to the first law (dq/dt = DC/h)
The following equation was put forth by Higuchi in 1962 for the situation where the medication dissolves. The Highuchi model, also referred to as the simplified Higuchi model, can be typically resumed to the following equation.
Ft = KHt 1/2
where KH is the Highuchi dissolution constant, which is occasionally handled differently by different authors and theories. According to Higuchi, drug release is a diffusion mechanism that is square root time dependant and based on Fick's rule.
Korsmeyer – peppas model
In 1983, Korsmeyer et al. created a simple, semi-empirical model that connected the drug release to the elapsed time (t) exponentially.
ft = atn
n is the release exponent, which indicates the drug release processes, t is Mt/M (fractional release of drug), and a is a constant that incorporates the structural and geometric characteristics of the drug dosage. The following initial and boundary conditions can be assumed if drug release takes place in a perfect sink condition:
t=0-d/2<x<d/z C=C0
t>0. x=+d/z= -d/z C=C1
The device's initial drug concentration is denoted by c0. The drugs concentration at the polymer-water interface is denoted by C1. A graph showing the amount of drug released under the specified conditions as a function of the square root of time should produce a straight line as diffusion is the primary drug release mechanism.
Table 1: Mathematical Models Used to Describe Drug Release Mechanism
|
S.NO. |
Mathematical model |
Equation |
|
1 |
Zero order |
Qt=Qo=kot |
|
2 |
first order |
In Q = in Qo + K1t |
|
3 |
higuchi |
Qt=KH√t |
|
4 |
Korsmeyer-peppas |
Qt/Q∞=Kktn |
15.Applications of Effervescent Tablets
• Improved stability and portability.
• A substitute for parenteral forms in situations when parenteral administration presents challenges.
• By adding small amounts of effervescent mixes to the tablet matrix, zero order release is accomplished.
• It works well in pulsatile systems; a fast-releasing core was created to ensure quick medication release upon polymer coating rupture.
• In floating medication delivery systems, the floating time is strongly influenced by the concentration of effervescent agents.
• For controlled release, effervescent osmotic pump tablets were employed.
• There were also cosmetic effervescent tablets available.
Enhancements brought on by effervescence include tight junction opening and an increase in the hydrophobicity of the intestinal membranes in rats and rabbits. [43]
16.Industrial application of effervescent tablets
17.CONCLUSION:
An important advancement in oral medication delivery methods, effervescent tablets provide a flexible and patient-friendly substitute for conventional solid dose forms. They facilitate quick disintegration, better palatability, and increased bioavailability by combining basic and acidic substances, which quickly produce carbon dioxide when they come into contact with water. These characteristics make them especially beneficial for elderly and pediatric patients, who frequently have trouble swallowing traditional tablets and capsules. Improved solubility for weakly water-soluble medications, efficient taste masking for bitter APIs, and a quick commencement of action since the formulation is pre-dissolved are just a few of the many advantages. Furthermore, by adjusting stomach pH, the buffered solutions produced by effervescent tablets might lessen gastrointestinal discomfort and promote improved absorption. These characteristics greatly increase patient compliance in addition to improving treatment efficacy. Not with standing their benefits, there are also issues, such as their susceptibility to moisture, the requirement for specific production and packing conditions, and the comparatively higher manufacturing costs. However, many of these issues have been successfully resolved by contemporary developments in formulation technologies including steam granulation, roller compaction, and fluidized-bed drying, opening the door for high-quality, scalable production. Furthermore, precise control and prediction of drug release profiles are made possible by the use of advanced release kinetic modeling, such as Higuchi, Korsmeyer-Peppas, and zero- or first-order kinetics. These models facilitate the creation of customized, controlled-release formulations that complement individualized treatment plans. Effervescent tablets are poised to become a mainstay in both therapeutic and preventative medicine due to the growing need for patient-centric dose forms and ongoing advancements in pharmaceutical technology. Beyond conventional medication therapy, they can be used in nutritional supplements, rehydration salts, and even cosmetic compositions. It is anticipated that as research advances, the use of innovative excipients and intelligent packaging methods will increase the usefulness and shelf-stability of effervescent systems. Effervescent tablets, in conclusion, are evidence of how careful pharmaceutical design can close the gap between patient convenience and clinical efficacy. They will probably play a bigger part in healthcare in the future, both in general medicine and in specialist treatments where accurate dosage, quick results, and easy administration are crucial.
REFERENCES
Shraddha Mali*, Nilesh Khutle, Sarita More, Swapnil Phalak, Formulation Science of Effervescent Tablets: From Manufacturing to Release Kinetics, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 5, 929-944 https://doi.org/10.5281/zenodo.15350690
10.5281/zenodo.15350690
