DJPS College of Pharmacy, Pathri Dist. Parbhani Maharashtra
Tablets remain one of the most widely used dosage forms in the pharmaceutical industry due to their ease of administration, stability, and cost-effectiveness. This review provides an in-depth exploration of the key aspects of tablet formulation, including the selection of excipients, the role of binders, fillers, disintegrants, and lubricants, and the processes involved in tablet manufacturing. The paper discusses the critical manufacturing steps, such as granulation, compression, and coating, while emphasizing the importance of controlling critical quality attributes like hardness, friability, dissolution, and uniformity. Challenges faced in tablet production, including issues of stability, bioavailability, and scale-up, are also addressed. Furthermore, the review highlights recent advancements in tablet technology, such as the development of novel formulations and the integration of automation and quality control measures. This comprehensive overview serves as a valuable resource for both researchers and industry professionals involved in the development and optimization of tablet dosage forms
Sustained release pharmaceuticals have emerged as a highly valuable tool in medical practice, offering patients a wide range of real and perceived benefits. Sustained release systems are also seen as a promising approach to minimizing medication side effects by maintaining a consistent therapeutic concentration of the drug in the body, preventing fluctuations. Traditional dosage forms of drugs are gradually being replaced by advanced and innovative drug delivery systems that offer improved therapeutic outcomes. In modern therapeutics, controlled release and sustained release dosage forms have gained immense popularity. Traditional dosage forms of drugs are gradually being replaced by advanced and innovative drug delivery systems that offer improved therapeutic outcomes. In modern therapeutics, controlled release and sustained release dosage forms have gained immense popularity. A matrix system is a type of drug delivery method designed to extend and control the release of a drug that is either dissolved or evenly distributed within the matrix material [1]. Among various routes of drug administration, the oral route remains the most commonly preferred due to its convenience, ease of use, and cost-effectiveness, making it the least e expensive option. Oral drug delivery is the most commonly used method for administering medicines, compared to other available routes for systemic drug delivery. It involves the use of various pharmaceutical products in different dosage forms. The main aim of drug delivery is to maintain a stable concentration of the drug in the systemic circulation which is both effective and safe for a prolonged period [2]. To achieve this, different dosage forms such as sustained release, prolonged release, controlled release, and timed release systems have been developed. These systems are specially designed to provide a continuous release of the drug over an extended period from a single dose. In the case of oral sustained-release formulations, the drug effect lasts for several hours depending on how long the drug stays in the gastrointestinal tract (GIT) [3].
Advantages: [4,5,6]
Disadvantages: [7]
Classification of Tablets: [8]
Depending on the route of administration or the function, the tablets are broadly classified as follows:
ii) Compression coated Tablet
Classification of sustained release drug delivery [9, 10]
Controlled release systems for oral administration are primarily solid dosage forms, with drug release regulated by dissolution, diffusion, or a combination of both mechanisms. Depending on the method of drug release, these systems are categorized as follows:
1. System of continuous release
2. Mechanisms of delayed transit and continuous release
3. Systems with a delayed release
1. Continuous release systems:
Continuous release systems provide sustained drug release throughout the entire gastrointestinal tract as the dosage form follows its normal transit path. The following are the different systems that fall into this category:
a. Diffusion controlled release systems
b. Dissolution controlled release systems
c. Diffusion and dissolution-controlled release systems
d. Ion exchange resin- drug complexes
e. pH-independent formulation
f. Osmotic pressure-controlled systems.
a. Diffusion controlled release systems:
The rate-limiting step in these systems is the diffusion of dissolved drug through a polymeric barrier. Since the diffusion path length increases over time as the insoluble matrix is steadily depleted of drug, the drug release rate is never zero-order. The regulated drug delivery systems are based on the diffusion of a drug molecule through a polymeric membrane.
b. Dissolution-controlled release systems:
Dissolution-controlled release is accomplished by reducing the drug’s dissolution rate in the GI fluids. This can be done by embedding the drug in an insoluble polymer or by coating drug particles or granules with polymer layers of varying thickness. The rate-limiting step in this process is the drug’s diffusion across the aqueous boundary layer. The drug’s solubility acts as the driving force for its release, which is resisted by the stagnant diffusion layer of fluid surrounding it. The equation below provides an approximation for the dissolution rate (dm/dt) :
dm/dt = ADS/h………….(1)
Where,
A = Tablet’s surface area
D = Diffusivity of the drug
S = Aqueous solubility of the drug
h = Thickness of the boundary layer
The two types of dissolution-controlled release are:
The medication is suspended in an insoluble matrix of swell-able hydrophobic or hydrophilic materials.
c. Dissolution and Diffusion Controlled release System
The API is enclosed in a partially soluble membrane of polymer. Pores are formed when sections of the membrane dissolve, allowing aqueous medium into the centre and thus drug dissolution, as well as the diffusion of dissolved drug out of the system.
d. Ion exchange resin-drug complexes:
It involves the creation of a drug-resin complex, which forms when an ionic solution interacts with ionic resins. The drug in this complex is exchanged in the gastrointestinal tract and released when there is an excess of Na+ and Cl present in most cases, an insoluble cross linked polymer resin is used in this system. They have a salt forming function group in a polymer chain that repeats.
e. pH-independent formulation:
Most drugs are weak acids or bases, which means their release from sustained-release formulations is influenced by pH. To maintain a stable pH and slow down pH-dependent drug release, a buffer, such as citric acid salt, amino acid, or tartaric acid, can be incorporated into the formulation. By combining a simple or acidic drug with one or more buffering agents, granulating with appropriate excipients, and coating with a gastrointestinal fluid-permeable, film-forming polymer, a buffer-retained release formulation is achieved. As gastrointestinal fluid passes through the membrane, the buffering agent changes the pH of the fluid within, resulting in a steady rate of drug absorption release.
f. Osmotic pressure-controlled systems:
A semipermeable membrane is placed around the tablet, particle, or drug solution to allow water to enter the tablet, with drug solution eventually being pumped out through a small delivery aperture in the tablet centered. There are two types of osmotic pressure-controlled systems: Type 1, which features an osmotic core containing the drug, and Type 2, where the drug is enclosed in a flexible bag, surrounded by an osmotic core. By optimizing the formulation and processing factors, an osmotic system can be developed to deliver a variety of drugs at a predetermined rate.
2. Continuous release and delayed transit systems: These are developed to keep them in the GI tract for a longer period of time after they have been written. This category encompasses mucoadhesive and size-based systems, which are designed to remain in the stomach and typically contain medications that are stable at gastric pH.
3. Delayed release systems: Due to the design of these systems, drug release is restricted to a specific location within the gastrointestinal tract (GIT). The following drugs can be incorporated into such devices.
The two types of delayed release system are
1) intestinal release systems.
2) colonic release systems.
Ideal properties of sustained release tablet [11,12]
It should be stable in the gastrointestinal fluid and appropriately absorbed orally
Tablet Manufacturing Methods [13,14]
Tablets are manufactured by wet granulation, dry granulation or direct compression method.
Processing steps
Wet granulation is a process where a liquid is added to a powder in a vessel with agitation, leading to the formation of agglomerates or granules. After drying, these granules are compressed to form tablets .
2) Dry Granulation
This technique does not involve the use of liquids. It begins with the formation of slugs, which are then screened or milled to create granules. These granules are subsequently compressed to form tablets.
3) Direct compression
The term direct compression is used to define the process by which tablets are compressed directly from powder blends of active ingredient and suitable excipients, which will flow uniformly in the die cavity & forms a firm.
Fig.: Processing steps required in tablet granulation preparation [13,14]
Steps in Tablet Manufacturing [15,16]
Tablet manufacturing involves several steps to convert raw materials into a finished solid dosage form. The steps ensure the uniformity, stability, and therapeutic effectiveness of the tablets.
1. Weighing and Dispensing
Accurate weighing of active pharmaceutical ingredients (API) and excipients is the first and most critical step to ensure uniformity of the dose.
2. Mixing and Blending
All ingredients are blended uniformly to achieve consistent distribution of the drug throughout the mixture.
3. Granulation
Granulation is done to improve the flow properties and compressibility of the powder blend. It can be done by:
• Wet Granulation
• Dry Granulation
• Direct Compression (without granulation)
4. Drying
Wet granules are dried to remove moisture content and achieve the desired hardness.
5. Sieving
The dried granules are passed through sieves to obtain uniform particle size distribution for better compression.
6. Lubrication
Lubricants, glidants, and anti-adherents are added to enhance the flow properties and prevent sticking during compression.
7. Compression
The final blend or granules are compressed into tablets using a tablet press machine to form tablets of the desired shape, size, and weight.
8. Coating (Optional)
Tablets can be coated to mask taste, control drug release, enhance appearance, or protect the drug from environmental factors.
9. Packaging
The finished tablets are packed in suitable packaging materials like blister packs or bottles to protect them from moisture, light
Sustained Release Tablet
It is defined as any drug or dosage form modification that prolongs the therapeutic activity of drug [17]. In theory, tablets provide the most cost-effective method for achieving sustained and controlled drug release in solid dosage forms. At present, most products are made by placing coated pellets inside capsules. This method of sustained release offers several benefits, such as controlled emptying of particles from the stomach, the ability to apply different types of coatings, and the development of release profiles suited for different drugs. This system allows for an initial release of the drug, followed by a slower, sustained release. However, tablets with a slow-releasing matrix cannot always achieve these characteristics. Therefore, due to consumer expectations (and those of marketing specialists), controlled-release products are mostly available in capsule form. Only a limited number of sustained-release products are available in tablet form [18].
Sustained Release Drug Delivery System:
A sustained-release drug product is a dosage form specifically designed to release a drug at a controlled rate, maintaining a consistent drug concentration in the bloodstream over a defined period of time. Typically, such formulations deliver an initial therapeutic dose, followed by a gradual and sustained release of the drug . These systems offer several advantages, including improved bio availability, ease and convenience of administration, enhanced drug stability, maintenance of steady plasma drug levels, reduced gastrointestinal irritation and side effects, and minimized toxicity. However, sustained-release systems also have certain drawbacks. The release rate can be influenced by various factors such as food intake and gastrointestinal transit time. Additionally, they tend to be more expensive, may lead to drug tolerance or "dose dumping," are subject to extensive first-pass metabolism, and often show poor in vitro–in vivo correlation .[19,20,21,22]
Mechanism of Sustained Release Tablets
Sustained release tablets control the drug release rate through different mechanisms to maintain therapeutic drug levels for an extended period. [23,24,25]
Mechanisms:
In this drug diffuses slowly through a polymer membrane or matrix. The rate of drug release depends on the concentration gradient. Diffusion controlled system falls under two categories
The semipermeable membrane of the tablet allows water to enter inside; the pressure created release the drug
The tablet matrix gradually erodes in the gastrointestinal tract, releasing the drug. This is ideal for biodegradable polymers.
Advantage tablet of Sustained release [26]
Classification of sustained release tablet [27]
1)Diffusion controlled release system
2)Dissolution controlled release system
3)Dissolution and diffusion controlled release system
4)Ion exchange resin drug complexes
5)pH – independent formulation
6)Osmatic pressure controlled system
Significance of sustained release tablets
Sustained release tablet play a vital role in modern drug delivery systems by offering several therapeutic advantages over conventional dosage form. The primary significance lies in their ability to maintain a consistent concentration of the the drug in the bloodstream over an extended period, reducing the frequency of drug administration. This ensures better patient compliance and convenience, particularly for chronic diseases that require long-term treatment. Moreover, sustained-release tablets help minimizes fluctuations in plasma drug levels, reducing the risk of side effects and toxicity linked to peak drug concentrations. These systems also enhance the therapeutic efficacy of drug by providing controlled and prolonged action at the target site. Furthermore, sustained release formulations reduce the overall cost of treatment by lowering the number of doses required and improving the efficiency of the drug molecule. This approach is especially beneficial for drugs with short biological half-lives, as it prolongs their activity and provides better management of disease conditions [28,29,30]
Tablet ingredients:
Besides the active ingredients, the tablet also contains various inert substances known as additives or excipients. Different excipients are:
Table No. 1: Tablet ingredients with examples
|
Sr No. |
Ingredients |
Example |
|
1 |
Diluents[31] |
calcium Phosphate; Carboxymethylcellulose Calcium; Cellulose; Dextrin; Lactose; Microcrystalline Cellulose; PR gelatinized Starch; Sorbitol; Starch |
|
2 |
Binders[31] |
Acacia; Alginic Acid; Carboxymethylcellulose; Cellulose; Dextrin; Gelatin; Liquid Glucose; Magnesium Aluminum Silicate; Maltodextrin; Methylcellulose; Povidone; Sodium Alginate; Starch; Zein. |
|
3 |
Lubricants[32] |
Calcium Stearate; Glyceryl Palmitostearate; Magnesium Oxide; Poloxamer; Polyvinyl Alcohol; Sodium Benzoate; Sodium Lauryl Sulfate; Sodium Stearyl Sulfate; Stearic Acid; Talc; Zinc Stearate |
|
4 |
Glidants[31,32] |
Magnesium Trisilicate; Cellulose; Starch; Talc; Tribasic Calcium Phosphate |
|
5 |
Anti – adherents[33] |
Corn Starch; Metallic Stearate; Talc |
|
6 |
Disintegrants[33,34] |
Alginic Acid; Carboxymethylcellulose; Cellulose; Colloidal Silicon Dioxide; Croscarmellose Sodium; Croscarmellose; Potassium Polacrilin ; Povidone |
|
7 |
Coloring agents[34] |
FD&C or D&C Dyes or Lake Pigments |
|
8 |
Flavoring agents[35] |
Ethyl Maltol; Ethyl Vanillin; Menthol; Vanillin |
|
9 |
Absorbents[35] |
Kaolin; Magnesium Aluminum Silicate; Tricalcium Phosphate |
|
10 |
Polymaers[36] |
Poly vinyl Pyrrolidone (Pup): Polyvinyl Alcohol (PVA): Polyethylene Glycol (PEG); Polylactic Acid (PLA); Polyglycolic Acid (PGA): Polycapprolactone (PCL); Polydioxanone suture (PDS); Polyetherurethane (PEU): cellulose Acetate (CA): Ethyl cellulose (EC); Polyvinyl chloride (PUC); Poly (2-hydroxyethyl methacrylate (PHEMA); Guar Gum : Gum Arabic Tragacanth |
Diluentare fillers used to make required bulk of the tablet when the drug dosage itself is inadequate to produce the bulk. Secondary reason is to provide better tablet properties such as improve cohesion, to permit use of direct compression manufacturing or to promote flow [31].
A diluent should have following properties:
To form cohesive compacts for directly compressed tablet [31].
Lubricants are used to prevent tablet materials from sticking to the surfaces of dies and punches, as well as to decrease friction between particles and may improve the rate of flow of the tablet granulation [32].
Glidants are intended to promote flow of granules or powder material by reducing the friction between the particles [31,32].
Anti-adherents are added to the tablet formulations to prevent the material from sticking to the walls of the tablet press [33].
Added to a tablet formulation to facilitate its breaking or disintegration when it contact in water in the GIT [33,34].
The use of colors and dyes in a tablet has three purposes: (A) Masking of off color drugs (B) Product Identification (C) Production of more elegant product [34].
Flavoring oils are needed for chew-able tablets. The oil is generally added in a dry form such as spray-dried bead-lets [35].
The inclusion of absorbents in a tablet formulation is necessary if the product contains a substance with a high affinity to water. Hygroscopic materials, if present, render the blend wet and difficult to handle during manufacture [35].
Resin a film-forming bio-polymer and its byproducts broadly form used for film coating and micro-encapsulation materials to accomplish sustained drug release [36].
Various types of polymers are -
1.Hydrogels- PHEMA, PUA PVP
2.Soluble polymers- PEG, PVA, PUP
3.Biodegradable Polymers - PLA, PGA, PCL.
4.Non-Biodegradable polymers - PEU, PDS, PUA
5.Muco adhesive Polymer- PUC, EC, CA.
6.Natural Gums - Gum Arabic, Guar gam, Tragacant [36].
Evaluation tests for sustained release matrix tablet [37,38,39,40]
These dosage forms were evaluated in two different methods.
I. Evaluation of granules
II. Evaluation of tablets
I. Evaluation of granules
i. Angle of repose [37].
The funnel technique was used to calculate the angle of repose. A funnel was fixed to a platform at a specified height (h) above horizontally arranged graph paper. The test was spilleduntil the funnel's point reached the summit of the conical bulk. Following measurements of the cone pile's radius and a calculation of its angle of repose
tan(θ) = height/radius of the heap.
ii. Bulk density [37]
The equation was used to establish the bulk density.
pb = MV
Where, pb = Bulk density, M = Mass of the granules in gm, V = final untapped volume of granules in ml
iii. Tapped density [37,38]
The tapped density was measured using the equation
pt = M / V P
Where, p t = true density
M = Mass of granules in gm.
VP = Final tapped volume of granules in ml
iv. Compressibility index [38]
The capacity of powder to be compacted was evaluated; consequently, the proportional significance of inter-particulate interactions was observed. The compressibility index was calculated by following equation
Compressibility index= (Dt-Db) x 100
Where,
Dt=Tapped density,
Db=Bulk density
v. Hauser's ratio [38]
It was calculated by the following equation
Hauser's ratio= Dt/Do
Where,
Dt =Tapped density,
Do= Bulk density
II. Evaluation of tablets
Using an electronic scale, 20 tablets of each formulation were measured to investigate weight variance, and the test was carried out by the recommended procedure.
ii. Friability test [39]
Twenty pills were weighed and included in the Roche friabilator, which was then spun at a speed of 25 revolutions per minute for four minutes. The tablet was weighed and cleaned after the revolt.
% friability= Wo - W/Wo x 100
Where,
Wo = Initial weight of twenty tablet
W = weight of 20 tablets after 4 minutes
iii. Hardness test [39,40]
Using a Monsanto hardness tester, six tablets were examined for hardness from each batch. An average of six values was recorded along with the standard variation for each batch, as well as the hardness of the individual tablets.
iv. Thickness test [40]
Twenty tablets were randomly selected from the collection, and the thickness of each tablet was measured. Six tablets from each batch were inspected, and the average width and standard deviation values were calculated.
v. In-vitro drug release [40]
Formulated tablets were put through an in vitro dissolving test using a paddle-style USP type 1/device running at 100 revolutions per minute and maintaining a 37°C water bath. Dissolution was maintained in 900 ccs of simulated stomach fluid for two hours and in simulated intestinal fluid for an additional eight hours. A UV-visible spectrophotometer was used to detect the emission of various medications at specific wavelengths over time.
RESULT & DISCUSSION:
This review highlights the classification, formulation ingredients, and evaluation parameters involved in tablet development. Tablets remain the most preferred oral dosage form due to their stability, ease of administration, accurate dosing, and patient compliance. Various types of tablets, including immediate-release, sustained-release, chewable, effervescent, and orally disintegrating tablets, were discussed in terms of their formulation objectives and functional excipients. The review reveals that the choice of excipients plays a critical role in determining tablet characteristics such as disintegration time, hardness, friability, and dissolution profile. Superdisintegrant, for instance, significantly enhance the disintegration and dissolution rate, improving bioavailability, especially in immediate-release formulations. On the other hand, hydrophilic matrix-forming agents and polymers are essential in sustained-release systems to control the drug release kinetics. Evaluation parameters such as hardness, friability, weight variation, disintegration time, and in vitro drug release are essential for ensuring product quality and consistency. Overall, the discussion underscores the need for a well-balanced formulation strategy that considers both the physicochemical properties of the drug and the desired release profile. Continued research and innovation in tablet formulation and processing techniques are expected to further enhance the efficacy and patient compliance of oral drug delivery systems.
REFERENCES
K. A. Tengse, R.D. Ingole, P.D. Hajare, S.D. Sakhare, N.S. Chavan, R.M. Bhapkar, S.G. Awate, D.H. Ubale, Advancements in Tablet Technology: A Review of Formulation, Process, and Quality Assurance, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 6, 2651-2663. https://doi.org/10.5281/zenodo.15654153
10.5281/zenodo.15654153
