A Comprehensive Study on Pharmaceutical Mini Tablets and Pellets
Jyothi G*, Ujwal Kamavarapu, Harika Muthyala, Sudhakar M
Department of Pharmaceutics, Malla Reddy College of Pharmacy, Hyderabad, Telangana, India - 500100.
*Corresponding Author E-mail: gattujyothireddy@gmail.com
ABSTRACT:
Mini tablets provide several benefits, including being very simple to make, requiring fewer coating ingredients, and having a lot of formulation development freedom. Children and older people like little tablets because they are simpler to swallow. Reduced dosage frequency and improved localization of the drugs are the objectives of controlled drug delivery systems are impacted. Mini tablets provide improved homogeneity and reduce variability in drug release among subjects, increasing the consistency and predictability of treatment. Some scaled-down tablets are accessible, like bio-adhesive, pH-responsive, purgative, pediatric, and oral deteriorating mini tablets. If any kind or explicit clinical requirements, they are intended to meet the patient's necessities. Different strategies for delivering circles, like direct compaction, wet granulation, or dry granulation, are contingent upon the result's ideal properties. Coatings in little vials can be utilized for different purposes, like flavour coatings, dampness or light security, or coatings of altered synthetic substances. The determination of coatings relies upon similarity with the dynamic fixing and the ideal delivery rate. The current article comprehensively reviews the dosage, types, manufacturing and analysis methods, benefits and challenges of the mini tablets, and recent technological advances.
KEYWORDS: Mini tablets, Pellets, Types, Dosage, Making.
INTRODUCTION:
A new advancement in solid dosage form design is the development of mini-tablets, which aim to solve critical therapeutic issues, including polypharmacy therapy, swallowing difficulties, dose flexibility and mixed release patterns. Mini-tablets are a potentially efficient medication administration technique that is patient-friendly. Tablets of 2-3 mm or less in diameter are called "mini-tablets". The tabletting of mini-matrices is a desirable substitute for creating pellets because it avoids using solvents (such as water) and results in high production yields comparable to extrusion and spheronization1. Additionally, the production technique simplifies producing items of a specific size and strength, with slight variation across batches2,3.
Mini tablets offer a broad application zone and can be plane or slightly curved. Their diameter ranges from 3-6 mm or less. They are frequently included in capsules for convenience. Still, they can also be compacted into bigger tablets or put into sachets after dissolving, releasing these subunits as various unit dose forms. Ingenious or rotating tablet presses manufacture mini tablets utilizing several punches. Because they can be quickly made and transformed into regulated medication delivery systems, mini-tablets are excellent alternatives to granules and pellets. To manage medication release, mini-tablet development is a crucial area of research in controlled-release4,5 solid dosage methods6,7,8,9. With less covering material than granules, the covering is more reproducible because of their decent size, solid mechanical characteristics, consistent explicit surface region, smooth external surface, and little variety inside and between groups. Mini tablets have various benefits over single-unit measurement structures, including a generally safe portion unloading and freedom from the planning of feast conveyance10.
Due to their improved gulping and adaptable dosing, consolidating different delivery energy, portions, and dynamic mixtures in a solitary framework, mini tablets (covered or uncoated and single-or various unit frameworks) are evolved as tolerant cordial frameworks for pediatric and geriatric patients as well concerning customized medication. Additionally, mini-tablets can be used successfully as multiple-unit modified release systems11,12 (extended-release, delayed-colon release, pulsatile and bi-modal release, and gastro-retentive systems), which increase medicine bioavailability compared to traditional tablets—using systems with a single unit9,13. The current article comprehensively reviews the dosage, types, manufacturing and analysis methods, benefits and challenges of the mini tablets, and recent technological advances.
The following techniques can be utilized to make mini tablets:
a) Direct compression
b) Dry granulation
c) Wet granulation
d) Melt-extrusion.
Mini tablet production frequently uses the direct compression technique. This technique creates tiny tablets by compressing a powder mixture containing excipients and pharmaceutically active substances. The excipients' quality, mainly those made for direct compression, determines how rugged the tablets are. The process involves filling a die with the powder blend and applying high pressure using upper and lower punches in a tablet machine. This compression step transforms the powder into mini tablets. One of the ease and efficacy of the direct compression method, which does not require additional processing stages, is its advantages.14
Especially for heat- and moisture-sensitive medications, the dry granulation process effectively produces micro tablets. Slugging, a procedure, is used in this method to create granules15. The central processing tool for this approach is a roller compactor. Premixed powders are positioned between two counter-rotating rollers in the dry granulation process. and subjected to high pressure. The intense pressure causes the powders to compact and form mini tablets. The small tablets' integrity and uniformity are improved with this technique. The dry granulation method is particularly beneficial for drugs that cannot withstand the heat and moisture involved in wet granulation methods. It allows for the production of mini tablets without liquid binders or solvents, reducing the risk of degradation or loss of potency in moisture-sensitive or thermo-labile drugs.16
The wet granulation method is another standard method for small spheres. This method forms granules by thoroughly mixing reactant, catalyst, and disintegrant. These granules are then pressed into small balls using a rolling pin. The main component of the wet granulation method is the binder which is responsible for holding the granules together and ensuring the uniformity of the small spheres. Various polyvinyl pyrrolidine (PVP) are commonly used as binders in this method. PVP is a water-soluble polymer that can efficiently bind particles together, making the particles cohesive during wear. The wet milling method offers many advantages. It helps improve the flow and compressibility of powders, improving bullet quality. Smaller chemicals may also include hydrophobic or poorly soluble chemicals. Also, using PVP and other binders helps increase the mechanical strength and stiffness of small spheres.17,18
The Melt-Extrusion Technique is a process that is used to make tiny tablets. This method involves creating a premixed powder that contains both the medication and the excipients. After that, a dissolving extruder is fed with the premixed powder, where it melts. Within the material's melting point range, parameters, including temperature, screw speed, and feed rate, are precisely regulated. During a melt-extrusion process, the material is melted and mixed thoroughly. The melted material is then extruded and formed into granules. These granules are further processed and sieved to obtain uniform-sized particles. Once the granules are obtained, they can be crushed by a compression device into tiny tablets. The compression process involves applying pressure to the granules, which results in the formation of compact mini tablets. The melt-extrusion technique offers several advantages. It allows for incorporating heat-sensitive drugs or poorly water-soluble drugs into mini tablets. The controlled melting process ensures uniform mixing of the drug and excipients, leading to enhanced drug dissolution and bioavailability19,20.
By the target site, the following categories of patient demands and production methods are identified:
a. pH-responsive mini tablets
b. Gastro retentive min tablets
c. Paediatric mini tablets
d. Bio-adhesive mini tablets
e. Oral disintegrating mini-tablets
Drugs released from pH-responsive mini tablets in reaction to variations in the pH of the gastrointestinal tract. Variable regions of the digestive tract have extremely varying pH levels. Hence pH-responsive drug delivery systems are necessary to deliver drugs to
specific locations and regulate stomach acid levels in a very acidic environment with a pH of 1.5 to 3. Small pH-sensitive pills use a medium made of Eudragits and other pH-sensitive polymers that prevent the stomach from dissolving the pill as the particles reach the pH rise from 4.0 to 5.0 in the duodenum, the top portion of the small intestine. The pellets' pH-sensitive coating starts to dissolve or degrade at this pH, releasing the medication20. In the jejunum and ileum, the lower portion of the small intestine, pH increases further from 6.5 to 7.5. Under this neutral condition, the pH-sensitive coating dissolves or decomposes, facilitating drug release. The pH of the colon ranges from 5.6 to 6.9. When there is slight acidity in the colon, the coating melts or decomposes, releasing drugs, especially in this area.21
The purpose of gastro retentive mini tablets, sometimes called floating mini tablets, is to absorb and hold the medication in the stomach for extended periods. These tablets float above the gastric mucosa, allowing the medication to the stomach longer. Aerosols are added to the tablet formulation to make it more conductive. When these chemicals react with gastric juices, they produce gas, usually carbon dioxide (CO2). The trapped CO2 gets absorbed into the evaporated water, allowing longer in the stomach by allowing the tablet to float 18. This method involves suspending small doses in an aqueous bed and coating the solution with an evaporative layer using a controlled process. The use of smaller laxatives can delay gastrointestinal infusion. The buoyant ability of these small molecules allows for prolonged drug delivery to the gastrointestinal tract, which may be helpful for drugs that require localized action or are poorly absorbed in the intestine.22,23
The use of pills, capsules, and syrups are prescribed by pediatricians every day. However, there are various difficulties with these traditional doses when used in children. Drugs can be challenging in terms of dosage, as they are often large and difficult to swallow. Breaking down the drugs to get the desired dosage can compromise the integrity and effectiveness of the drug. Patient compliance is also a concern, as children may resist taking the drug. Syrups, on the other hand, offer ease of administration and allow the dosage to be adjusted to suit the patient's needs. However, syrup also has its drawbacks.
Taste issues can make it challenging to ensure that children consume the total dose and are susceptible to microbial, chemical, and metabolic instabilities24. Mini pills are generally the favoured option for children since they are simple to administer, promote patient adherence, and can potentially address the shortcomings of other dose forms, including capsules, tablets, and syrups. By formulating medications in mini-tablets, healthcare professionals can ensure better acceptance and adherence to treatment regimens in paediatric patients.25
Vaginal administration presents complications with traditional formulations such as ointments, lotions, and gels. These medications tend to be aggressive, have frequent leaks, have limited shelf life, and may lead to low patient compliance. While Nano chemicals offer a potential solution, short shelf life due to their liquid nature remains a concern. Bio-adhesive polymers are used to overcome these challenges26. Bio-adhesive mini tablets offer advantages in vaginal drug delivery by providing extended release, better bioavailability, and improved patient compliance. They circumvent the drawbacks of conventional dosage forms and enable precise and controlled drug distribution in the canal of the vagina.
Oral dispersion tablets (ODTs), commonly referred to as oral dissolving micro tablets, are specialized drug delivery solutions that rapidly dissolve in the mouth within 1-3 minutes without the need for swallowing or chewing. They offer many benefits over tablets with the use of conventional oral solids. ODTs are sometimes called dispersion, oral dispersion, rapid dissolution, rapid dissolution, spherical, rapid dissolution, or oral dissolution ODTs are particularly suitable for pediatric patients because they have a pleasant oral feel, dissolve rapidly in the mouth, and are smaller than conventional drugs. There are specific properties that ODT must possess27.
First, they must disintegrate in the palate without additional fluids. Once it disintegrates, the drug should be converted into a liquid concentrate or viscous tablet, which allows for better swallowing and better mouthfeel because ODT disintegrates or disintegrates. As a result, the medicine is notably reduced close to the target in the patient's mouth. Therefore, having a pleasant taste in the mouth is crucial for developing tolerance. To make a product more palatable, taste masking techniques should be utilized if it has an unpleasant flavour. The flavour coating technology must be compatible with the ODT formulation.28
|
Advantages |
Description |
|
Efficient Production |
Small pills can be manufactured efficiently and in large quantities. |
|
Homogeneous Size |
Mini tablets are exceptionally uniform in size, have smooth surfaces, and are well-formed. |
|
Consistent Size and Weight |
Small pills exhibit uniformity in size and weight, making them easy to produce. |
|
Stacking Tolerance |
Mini pills have a generous tolerance for drug stacking, contributing to manufacturing reliability. |
|
Solvent-Free Production |
Production of tiny tablets requires fewer solvents, reducing concerns related to solvent usage. |
|
Batch-to-Batch Consistency |
Minimal batch-to-batch variations, especially when compared to other Multi-Unit Dosage Forms (MUDFs). |
|
Extensive Drug Loading |
Mini tablets are designed to accommodate high drug loading, various release rate patterns, and precise tuning of release rates. |
|
Repeatability |
Mini tablets offer high repeatability in their characteristics, reducing variability between and within subjects. |
|
Reduced Variability |
Lower inter- and intra-subject variability contributes to consistent drug delivery. |
|
Lower Risk of Dosage Dumping |
Mini tablets present a lower risk of dosage dumping, enhancing safety during administration. |
|
Advantages in Paediatric Medicine |
Sustained-release mini-tablets can offer benefits in pediatric medicine, such as masking taste, altering release patterns, and aiding swallowing due to their small size. |
Mini Tablets formulation studies:
Physical and analytical profiles are described in pre-formulation investigations to create stable pharmacological dosage forms. Defines the flow features: the ability to compress index, Hauser's ratio, volumetric density, tapped density, angle of repose, and Studies on the compatibility of drug excipients: FTR and DSC.
i) Degree of repose: The powder mixture was measured out, added to the funnel, and allowed to flow through until a pile of paper formed at the bottom. The pile's height (h) and the cone's width were calculated. The radius (r) was computed using the diameter. The following conditions can be utilized for calculating the inclination of repose.
Ɵ = tan̵ 1 (h/r)
Where h = height of pile r = radius of the base of the pile
ii) Bulk density: The mixed blend's volume in Bulk is measured using a measuring cylinder. Using the formula that follows, the Bulk density can be calculated.
Bulk density (BD) = Mass of the mix / Bulk volume of the mix
iii) Tapped density: The amount of powder mixture placed in the cylinder with the graduated shape and tapped 500 times is weighed to determine the tapped density. The formula below is used to calculate tap density.
Tapped density (TD) = Mass of mix/ Tapped volume of the mix
iv) Compressibility index: The compressibility index shows how likely an ingredient is to bind. The mix's stream characteristics are displayed. The degree of compressibility index was determined based on observations of the Bulk and tapped densities.
Compressibility index= (TD-BD) ×100/TD
Where TD = Tapped density BD = Bulk density
v) Hausner's ratio, calculated by the ratio of the tapped density to the Bulk density, describes the stream properties of the powdered mix.
Hausner’s ratio = Tapped density/Bulk density
vi) FTIR studies: IR spectra for pure pharmaceuticals and micro tablet forms were analyzed in an FTIR spectrophotometer.
vii) DSC studies: differential scanning calorimetry (DSC) investigations were finished for the optimal minitablet compositions and the purest medication. All sample analyses were conducted using perforated and sealed aluminium pans. Utilizing indium as the reference, heat calibrations were put into practice. An empty pan that had been sealed similarly to the sample was used as a guide. The entire set of samples was taken at a scanning rate of 100C/min between 50 and 3000C.
Evaluations following compression:30,31
viii) Weight variation: A sophisticated weighing balance is used for the weight variation test. Twenty mini tablets were picked randomly, and the average weight was determined by weighing each individually. The formula below was used to calculate the proportion of the weight variation:
% Weight variation = (Individual weight – Final weight)/Final weight X 100
ix) Hardness: The hardness of each mini tablet formulation was calculated using a Monsanto hardness tester. kg/cm2 is the unit of measurement. A tablet's hardness is determined by how much power is required to break it. Six micropillars from each formulation, chosen at random, were used to compute the averages and standard deviations.
x) Thickness: Using a digital calliper and screw gauge, the thickness of ten randomly chosen mini pills from each formulation was recorded separately in mm. The standard deviation and mean values were determined by computations.
xi) Friability: Twenty micro pills are randomly chosen from each composition, and their starting weight (W0) is recorded and put in a friability. After the tiny tablets were removed, the friability apparatus was rotated for 4 minutes at 25 rpm. Weighing again (Wf) for little tablets. The following formula was used to determine the percentage of friability.
% F = (W0 – Wf) /W0X 100
Whereas, % F = Percentage of friability; W0 = Initial Weight; Wf = Final weight
xii) Disintegration: Using a breakdown test apparatus in accordance with Indian Pharmacopoeias guidelines, the disintegration time of micro tablets was calculated. Each of the basket's six tubes contained one little tablet. A dissolution medium immersion liquid in the amount of 900 ml was used to operate the apparatus. In a dissolution medium that was kept at 370C, the assembly was elevated and lowered 30 times per minute. Then record the duration of the small pills' breakdown.
xiii) Drug Content: In order to precisely weigh five little tablets and smash them in a mortar, the drug content was ascertained. Then the amount of powder was measured. A 100 ml volumetric flask containing 100 ml of solvent and 5 mg of the medication was added. To liquefy the medication, the flasks were shaken. A UV visible spectrophotometer was used to analyze 1 ml of the aforementioned solution after diluting it by 10 ml and performing the examination at lambda max. Using UV concentration readings, calculate the drug content.
xiv) In Vitro Dissolution Studies: Studies on in vitro dissolving were conducted using the USP dissolution type 1 (basket) apparatus for mini tablets enclosed in capsules and type 2 (paddle) apparatus for micro tablets compressed into large tablets. Three distinct dissolving media were used, each with a different pH buffer (pH 1.2 for the stomach, pH 6.8 for the intestine, and pH 7.4 for the colon) to imitate the pH shifts that occur in the gastrointestinal tract. Throughout the analysis, the temperature of the dissolving media was maintained at 37°C, and the rotation speed of the basket or paddle was maintained at 50 rpm. Each time, 900 millilitres of the dissolving medium were utilized. In tests for controlled release or delayed release dosage forms, 0.1 N HCL was used for the first two hours, while the average gastric emptying time is two hours. Then, the medium used for dissolution was discarded, and a new dissolution medium at pH 6.8 phosphate buffer was added for three hours. Finally, the pH 6.8 buffer was discarded, and a new dissolution medium at pH 7.4 phosphate buffer was added for the remaining time (24hours). At certain times, 5ml of the dissolution medium was removed, and new dissolution medium was substituted. By using a UV-visible spectrophotometer to analyze the withdrawn samples, it was possible to calculate the aggregate quantity of medication released during the collection periods.
Pellets: A Potential Multi-Particulate System Candidate
Pellets certainly stand out in the field of drug research as an expected possibility for multi-particulate medication conveyance frameworks. These little, circular or almost round strong particles offer a scope of benefits that make them exceptionally reasonable for different drug applications. One key benefit is their capacity to give controlled drug discharge, taking into account supported restorative activity and working on quiet consistency. Furthermore, pellets display upgraded bioavailability contrasted with customary measurement structures because of their multi particulate nature, which builds the surface region accessible for drug ingestion. This can prompt better restorative results and possibly lower required drug doses. The adaptability in the detailing is one more engaging part of pellets. They can be tweaked to oblige different medication substances and delivery profiles, giving custom-made drug conveyance procedures. Besides, pellets diminish the gamble of portion unloading, guaranteeing a more controlled and steady arrival of the medication. They additionally exhibit work on gastric maintenance, which is helpful for specific plans requiring delayed home time in the gastrointestinal plot. Ultimately, the adaptability of pellets in measurement structures considers the simple organization and exact dosing, offering choices like cases, tablets, or granules. Generally, pellets display extraordinary qualities that make them a promising contender for multi-particulate medication conveyance frameworks, introducing new open doors for enhanced treatments and working on understanding results.32
Utilizations of Pellets in Multi-Particulate Frameworks:
Pellets have arisen as an expected contender for multi-particulate medication conveyance frameworks, tracking down a large number of utilizations in the drug business. Their interesting attributes and benefits make them exceptionally flexible for different restorative purposes.
Supported Delivery Definitions:
One critical use of pellets in multi-particulate frameworks is the improvement of supported discharge definitions. By integrating drugs into pellets with controlled discharge properties, supported discharge plans can be accomplished. These details step-by-step discharge of the medication over a drawn-out period, keeping up with remedial levels in the body and decreasing the recurrence of dosing. Pellets take into consideration exact command over the delivery rate, empowering the advancement of supported discharge items for ongoing circumstances or meds that require delayed activity.33
Mix Treatments:
Pellets offer a promising methodology for the improvement of mix treatments inside multi-particulate frameworks. Numerous medications stacked pellets can be joined in a solitary plan, considering the concurrent conveyance of various dynamic drug fixings. This empowers the organization of mixed treatments, where at least two medications with corresponding activities can be conveyed together to upgrade adequacy, work on persistent consistency, and rearrange dosing regimens. Pellets give the adaptability to tailor the delivery profiles of individual medications, streamlining their remedial impacts and accomplishing synergistic results.33
Paediatric and Geriatric Details:
Pellets have earned respect for their reasonableness in paediatric and geriatric plans inside multi-particulate frameworks. These patient populations frequently face difficulties in gulping customary tablets or containers. By forming drugs into pellets, they can be integrated into age-proper dose structures like oral suspensions, sprinkle details, or orally breaking down tablets. Pellets give a great choice to exact dosing, as they can be precisely estimated and scattered, guaranteeing precise medication organization in pediatric and geriatric patients.32
Taste-Covering and Smell-Controlled Definitions
Undesirable taste and scent are normal issues experienced in specific medications, particularly in pediatric plans or meds with a solid trademark smell. Pellets offer a powerful answer for taste-veiling and smell-controlled plans. By typifying the medication inside pellets and giving a fitting covering, the taste and scent can be concealed, upgrading patient acknowledgement and consistency. This is especially valuable in the advancement of oral fluid suspensions, enjoyable tablets, or orally deteriorating definitions.34
Adjusted Delivery Frameworks:
Pellets are broadly utilized in the improvement of changed discharge frameworks inside multi-particulate plans. Altered discharge definitions mean to convey drugs at explicit locales in the gastrointestinal parcel or give pulsatile drug delivery to time-delicate treatments. By controlling the synthesis, covering, or centre properties of pellets, specialists can accomplish designated drug discharge, site-explicit ingestion, or pulsatile drug conveyance. Pellets' flexibility considers exact command over the delivery component, guaranteeing ideal helpful results.
In rundown, pellets offer different applications inside multi-particulate medication conveyance frameworks. Their utilization of supported discharge plans, mixed treatments, pediatric and geriatric definitions, taste-veiling and smell-controlled details, and altered discharge frameworks exhibits their adaptability and importance in drug advancement. Pellets give a stage to tweaked drug conveyance procedures, working on persistent consistency, restorative viability, and in general treatment results.17,35
Benefits of Pellets in Multi-Particulate Frameworks
Controlled Medication Delivery:
Pellets utilized in multi-particulate frameworks offer the upside of controlled drug discharge. By figuring out pellets with explicit delivery profiles, for example, supported discharge or designated discharge, scientists can accomplish exact command over the rate and length of medication discharge. This considers a more reliable and controlled restorative impact, guaranteeing ideal medication fixations in the body over a lengthy period.36
Upgraded Bioavailability:
Pellets show further developed bioavailability contrasted with single-unit dose structures. Their small size and expanded surface region empower quicker disintegration and assimilation of the medication. This upgraded bioavailability brings about more effective medication conveyance to the objective site, augmenting helpful viability while possibly diminishing the necessary measurement.
Diminished Chance of Portion Unloading:
Portion unloading, the unexpected arrival of a lot of medication from a measurement structure, can prompt unfriendly impacts or sub-par remedial results. Pellets, when integrated into multi-particulate frameworks, limit the gamble of portion unloading. Every pellet goes about as a singular unit with its own controlled delivery system, guaranteeing a continuous and reliable arrival of the medication, hence improving security and remedial viability.36
Adaptability in Definition: Pellets offer extraordinary adaptability in detailing plan. Different medication stacked pellets can be joined in a multi-particulate framework to accomplish wanted drug blends or delivery profiles. This adaptability considers the advancement of customized drug conveyance frameworks, including fixed-portion mixes, pulsatile discharge details, or successive delivery frameworks. It additionally empowers the fuse of various medications with shifting solubilities or soundness prerequisites, growing the opportunities for remedial development.37
Worked on Gastric Maintenance: Some medication plans to benefit from expanded home time in the stomach for ideal retention or restricted activity. Pellets, due to their multi-particulate nature, show further developed gastric maintenance contrasted with bigger single-unit dose structures. They scatter all the more consistently in the stomach, considering better circulation and delayed contact with the gastric mucosa. This upgraded gastric maintenance can upgrade drug retention and work on remedial results, especially for drugs that are retained fundamentally in the stomach or upper gastrointestinal plot.38
Techniques for Making Pellets:
1. Expulsion-Spheronization:
A wet mass, right off the bat, is ready by blending the medication and excipients with a cover arrangement. The wet Mass ought to have fitting rheological properties to guarantee appropriate expulsion and spheronization. The wet Mass is then taken care of into an extruder, where it goes through the expulsion interaction. The extruder comprises a turning screw that powers the wet Mass through a punctured plate, bringing about the development of barrel-shaped extrudates32. These extrudates are then gone through a spheronizer, which is a turning rubbing plate or a vault-formed chamber. The spheronization interaction includes the utilization of shear powers and impacts that separate the extrudates and round them into circular pellets. The spheroid pellets are then dried to eliminate dampness, and further handling steps, for example, screening and covering can be performed if fundamental. Expulsion spheronization offers a few benefits for pellet readiness. It considers exact command over pellet size and shape, guaranteeing consistency and reproducibility. The cycle can oblige a wide variety of medication substances and excipients, making it reasonable for different plans. Moreover, expulsion spheronization is a versatile and practical strategy, generally utilized in both examination and modern settings.1,32
2. Layering:
The layering system can be completed utilizing various strategies, contingent upon the ideal result and gear accessibility. One normal technique is air suspension, where the seed centres are fluidized in an air stream, and the medication arrangement or suspension is splashed onto them. The cycle is rehashed on numerous occasions, developing layers of medication and excipients until the ideal pellet size is accomplished. Another method is skillet covering, which includes putting the seed centres in a pivoting dish and applying the medication arrangement or suspension onto them utilizing a shower framework. The container pivots, taking into account the uniform dispersion of the covering material and the arrangement of layered pellets. Fluidized bed covering is one more methodology for layering, where the seed centres are suspended in a fluidized bed of air or gas. The medication arrangement or suspension is splashed onto the fluidized bed, bringing about the testimony of various layers on the seed centres37. Layering offers flexibility in pellet detailing, as it considers the fuse of various medications, coatings, or useful layers. This empowers the improvement of multi-particulate frameworks with customized drug discharge profiles, blend treatments, or taste-concealing abilities. The strategy gives adaptability in accomplishing explicit medication conveyance prerequisites and wanted helpful results.38
3. Splash Drying:
Splash drying is a generally involved strategy for the readiness of pellets, especially for drugs that are heat-touchy or require fast disintegration. This method includes the atomization of a medication arrangement or suspension into fine drops, trailed by the drying of these beads to frame circular pellets. The cycle starts by setting up a medication arrangement or suspension that is reasonable for shower drying. The arrangement or suspension is then atomized into a drying chamber utilizing a spout or a shower gadget. Inside the chamber, hot air is presented, making the drops dry quickly. As the dissolvable dissipate, strong particles are framed, bringing about the age of pellets39. Splash drying offers a few benefits in pellet planning. It takes into consideration high creation rates, making it reasonable for enormous scope fabricating. The method additionally gives command over the molecule size circulation, guaranteeing consistency and reproducibility of the pellets. Also, splash drying empowers the consolidation of intensity delicate medications, as the drying system happens rapidly, limiting openness to high temperatures.40
4. Cryo-pelletization:
Cryo-pelletization is a novel strategy utilized for preparing pellets, especially for drugs that are delicate to high temperatures or solvents. This method includes the freezing of a medication arrangement or suspension into pellets utilizing fluid nitrogen or a cryogenic medium41. The interaction begins by setting up a medication arrangement or suspension that is reasonable for cryo-pelletization. The arrangement or suspension is then atomized or trickled into a cryogenic shower, like fluid nitrogen, where it quickly freezes. The frozen drops are hence moved to a freeze-drying chamber, where the dissolvable is eliminated through sublimation, bringing about the development of pellets41. Cryo-pelletization offers benefits for the arrangement of sensitive medication definitions. By staying away from openness to high temperatures or solvents, this strategy helps save the honesty and solidness of intensity of delicate or dissolvable delicate medications. The subsequent pellets show great stream properties and can be additionally handled or covered on a case-by-case basis42.
Pellet Properties in Multi-Particulate Systems:
1. Consistency:
Pellets have an eminent quality of consistency with regard to estimating, shape, and medication content. During the pellet fabricating process, methods like expulsion spheronization or layering guarantee steady pellet size and shape, prompting uniform medication discharge. This consistency is vital as it takes into consideration exact dosing and unsurprising medication conveyance, adding to upgraded restorative results. Drug specialists and medical care experts can depend on the consistency of pellets while recommending and directing meds.43
2. Mixing Abilities:
The mixing abilities of pellets empower the definition of multi-particulate frameworks with altered drug blends or delivery profiles. Different medication stacked pellets can be mixed together, taking into consideration the formation of remarkable details custom fitted to explicit restorative prerequisites. This adaptability in mixing works with the improvement of mixed treatments, where different medications can be integrated into a solitary dose structure, upgrading comfort for patients and enhancing treatment regimens.44
3. Similarity with Excipients:
Pellets display similarity with a wide variety of excipients, which opens up potential open doors for detailed customization. Excipients like polymers, surfactants, pH modifiers, or delivery-controlling specialists can be integrated into pellet plans to accomplish wanted drug discharge profiles, upgrade soundness, or further develop bioavailability. This similarity takes into consideration the improvement of the medication detailing by choosing excipients that supplement the particular properties of the dynamic drug fixing (Programming interface) and the ideal remedial targets.45
4. Custom-made Medication Delivery Profiles:
Pellets in multi-particulate frameworks offer the benefit of fitting medication discharge profiles. By controlling variables like pellet pieces, covering procedures, or layering systems, drug researchers can accomplish different medication discharge designs. This adaptability takes into account the plan of prompt delivery pellets for quick medication beginning, supported discharge pellets for delayed helpful impact, or intestinal-covered pellets for designated conveyance to explicit districts of the gastrointestinal parcel. Fitting medication discharge profiles guarantee the improvement of medication treatment, obliging different patient requirements and ailments.32
5. Simplicity of Organization:
Pellets' small size makes them simple to direct to patients, adding to work on quiet consistency. They can be exemplified inside gelatin or vegan cases, packed into tablets, or even integrated into fluid suspensions. This flexibility in organization courses upgrades patient accommodation, especially for people who experience issues gulping traditional tablets. By giving elective organization choices, pellets work with medicine adherence and work on tolerant experience.41
6. Improved Security
Pellets, particularly when covered with defensive layers, display upgraded solidness contrasted with single-unit measurement structures. Coatings can give an obstruction that safeguards the medication from ecological factors like dampness, light, or pH changes. This assurance guarantees the delayed timeframe of realistic usability of the medicine and keeps up with drug viability all through the item's life expectancy. The upgraded solidness of pellets pursues them a dependable decision for drug producers and medical care suppliers, guaranteeing the conveyance of protected and successful meds to patients.
The different qualities of pellets in multi-particulate frameworks feature their worth and flexibility in drug applications. These attributes, including consistency, mixing capacities, similarity with excipients, custom-made drug discharge profiles, simplicity of organization, and improved dependability, add to the advancement of upgraded drug definitions and customized treatments. The usage of pellets in multi-particulate frameworks gives amazing chances to further developed treatment results and upgrade patient fulfilment.40
Pharmacokinetic characteristics of mini-tablet advantages compared to other formulation:
The pharmacokinetic advantages of mini-tablets compared to other formulations are considerable, offering a range of benefits that address various therapeutic challenges. This section discusses these advantages in detail.
1. Improved Swallowing and Patient Compliance:
Mini-tablets, with their small size (2-3 mm in diameter), are easier to swallow than larger tablets or capsules. This is particularly advantageous for patients who have difficulty swallowing conventional tablets or for paediatric and geriatric populations. The reduced risk of choking or discomfort encourages better patient compliance, ensuring that the prescribed medication is taken as intended.46
2. Dose Flexibility:
Mini-tablets offer a high degree of dose flexibility. They can be designed to contain precise doses of active pharmaceutical ingredients (APIs), allowing for accurate and customized dosing. This is especially important when administering medications with narrow therapeutic windows or when adjusting dosages for individual patient needs.
3. Multiple Drug Delivery Strategies:
The design of mini-tablets enables the incorporation of different drug delivery strategies within a single dosage form. Mini-tablets can be coated or uncoated and can be formulated as single-unit or multiple-unit systems. This versatility allows for various release profiles to be achieved, including extended-release, delayed-colon release, pulsatile release, bi-modal release, and gastro-retentive systems. This capability enhances drug bioavailability, leading to optimized therapeutic outcomes.35
4. Reduced Variability:
The manufacturing process for mini-tablets results in consistent size, shape, and mechanical characteristics. This uniformity contributes to reproducible drug release profiles and pharmacokinetics, reducing the variability often observed in traditional tablet formulations. This aspect is crucial for maintaining therapeutic efficacy and patient safety.
5. Potential for Combination Therapy:
Mini-tablets offer a platform for combining different active ingredients or varying doses of the same ingredient within a single dosage form. This is particularly valuable for patients who require polypharmacy, where multiple medications are prescribed simultaneously. The ability to combine drugs in one formulation simplifies medication administration and improves patient convenience.47
6. Tailored Release Profiles:
Through the manipulation of coating technologies and formulation techniques, mini-tablets can be designed to achieve specific release profiles. This is essential for optimizing drug delivery to match the desired therapeutic effect. For instance, drugs that require immediate release can be combined with those needing sustained release in a single mini-tablet formulation.
7. Enhanced Bioavailability:
Mini-tablets, especially those with modified-release properties, can enhance drug bioavailability compared to traditional tablet formulations. Controlled-release mini-tablets allow for a slower and more controlled release of the drug, leading to prolonged exposure to the active ingredient and potentially reducing the frequency of dosing.
In summary, the development of mini-tablets represents a significant advancement in solid dosage form design, offering several pharmacokinetic advantages over conventional formulations. These advantages include improved patient compliance, dose flexibility, diverse drug delivery strategies, reduced variability, potential for combination therapy, tailored release profiles, and enhanced bioavailability. The unique characteristics of mini-tablets make them particularly well-suited for addressing the needs of diverse patient populations and optimizing therapeutic outcomes.46
Advantages of mini-tablets in pediatrics & and geriatrics compared to other formulations:
Mini-tablets offer distinct advantages in paediatric and geriatric populations when compared to other formulations. These advantages stem from their unique characteristics and tailor-made features that cater to the specific needs and challenges faced by these patient groups.
Advantages in Paediatrics:
Many formulations like lollipops47 and chewing gums48 are prepared by keeping in view of paediatrics and mini-tablets excel due to their small size, aiding easy swallowing. This promotes medication adherence and accurate dosing adjustments for growing children. They can be taste-masked, overcoming taste aversion issues, and their potential for combining multiple medications simplifies treatment regimens. Overall, mini-tablets enhance paediatric medication experiences.35
1. Ease of Administration:
Mini-tablets, due to their small size and smooth surface, are easier for paediatric patients to swallow. This is a crucial factor as children often struggle with swallowing larger tablets or capsules, leading to medication non-compliance. The reduced risk of choking or discomfort improves adherence to prescribed treatments.
2. Dose Accuracy:
Paediatric patients often require smaller and precise doses of medications based on their weight or age. Mini-tablets can be formulated with accurate doses, allowing healthcare providers to fine-tune the treatment to match the child's therapeutic requirements effectively.49
3. Flexible Dosing:
Children's medication needs may change as they grow or respond to treatment. Mini-tablets provide the flexibility to adjust doses according to changing requirements, which is particularly important when dealing with rapidly changing paediatric physiology.
4. Combination Therapies:
Paediatric patients may require multiple medications simultaneously. Mini-tablets offer an excellent platform to combine different drugs or doses within a single dosage form, simplifying administration and improving treatment compliance46.
5. Taste-Masking Possibilities:
Mini-tablets can be coated to mask the bitter or unpleasant taste of certain medications. This is especially significant for paediatric patients who are more sensitive to taste and are likely to resist taking medications with unpalatable flavours.
Advantages in Geriatrics:
In geriatric care, mini-tablets offer tailored advantages. Their small size eases swallowing for seniors, enhancing adherence. Dose flexibility accommodates personalized needs, while controlled-release options match extended therapy requirements. Combining multiple medications in a single mini-tablet simplifies complex regimens common in the elderly. Overall, mini-tablets improve medication experiences for geriatric patients.50
1. Ease of Swallowing:
Similar to pediatric patients, geriatric individuals often face difficulties in swallowing large tablets. Mini-tablets with their small size provide a comfortable and safer alternative, reducing the risk of choking and ensuring proper medication intake.
2. Reduced Polypharmacy Challenges:
Geriatric patients often have complex medication regimens, leading to polypharmacy. Mini-tablets' ability to combine multiple medications in a single formulation simplifies dosing schedules and reduces the number of pills patients need to manage.46
3. Customized Dosing:
Geriatric patients may have altered physiological functions and require adjusted dosages. Mini-tablets allow for precise dosing tailored to the individual's needs, enhancing therapeutic outcomes while minimizing the risk of adverse effects.
4. Modified Release Options:
Many geriatric patients benefit from controlled-release formulations to maintain steady drug levels and reduce the frequency of dosing. Mini-tablets can be engineered for various modified-release profiles, ensuring consistent drug delivery and therapeutic effects.50
5. Patient Acceptance:
Geriatric patients may have preferences for smaller dosage forms that are easier to handle. Mini-tablets can be packaged in convenient blister packs or sachets, making them more manageable and improving patient acceptance.
6. Enhanced Medication Adherence:
Mini-tablets' user-friendly characteristics contribute to improved medication adherence among geriatric patients. When medications are easier to swallow and manage, patients are more likely to adhere to their prescribed treatment plans.50
Emphasize how to overcome the drawbacks & and disadvantages of mini-tablet:
Overcoming the drawbacks and disadvantages associated with mini-tablets is crucial to fully realize their potential as an efficient and patient-friendly medication administration technique. While mini-tablets offer numerous advantages, addressing their limitations is essential for ensuring optimal therapeutic outcomes. Here are strategies to overcome the drawbacks of mini-tablets:
1. Uniformity and Precision in Manufacturing:
One drawback of mini-tablets is the need for precise manufacturing processes to ensure uniform size, weight, and drug content. To overcome this, advanced manufacturing technologies, such as high-speed precision tablet presses and automated quality control systems, can be employed. These technologies enhance the consistency and reproducibility of mini-tablet production.47
2. Taste-Masking Techniques:
Mini-tablets might still have an unpleasant taste for pediatric or geriatric patients. To address this, taste-masking techniques, such as using flavor coatings or incorporating sweeteners, can be utilized. This improves patient acceptability and adherence, especially in populations sensitive to taste.
3. Combination of Formulations:
While the versatility of mini-tablets allows for combination therapies, challenges can arise due to drug compatibility and release profiles. Formulation scientists can overcome this by conducting thorough compatibility studies and optimizing the ratios of active ingredients. Customized coatings and matrices can be designed to achieve desired release profiles for each component.46
4. Modified-Release Challenges:
Achieving precise modified-release profiles in mini-tablets can be complex. Employing advanced formulation techniques like multi-layered tablet design or incorporating specific excipients can aid in achieving the desired release kinetics.
5. Packaging and Identification:
Mini-tablets' small size can make them challenging to handle and package, leading to potential errors in dosing or identification. Packaging solutions, such as blister packs with clear labeling, can address this issue. Including unique imprints or color codes on mini-tablets can also aid in proper identification.49
6. Patient Education and Counseling:
Overcoming the drawbacks of mini-tablets requires educating patients, especially in pediatric and geriatric populations. Healthcare professionals should provide clear instructions on how to take mini-tablets, emphasizing the importance of not crushing or breaking them if they are not designed for such administration.
7. Technological Innovations:
Continued research and technological advancements can further overcome the limitations of mini-tablets. Innovations in nanotechnology, 3D printing, and personalized medicine can contribute to enhancing their effectiveness, bioavailability, and patient acceptance.46
8. Regulatory Considerations:
Overcoming the challenges associated with mini-tablets also involves adhering to regulatory guidelines for quality, safety, and efficacy. Collaboration between pharmaceutical companies and regulatory authorities can help ensure compliance and address potential concerns.46
In conclusion, when compared to single-unit dosage forms, pharmaceutical mini tablets offer precision dosing, prevention of local irritation and dose dumping, and enhanced bio adherence. They are advantageous for paediatric and elderly individuals and are particularly helpful for medications absorbed in the small intestine. Additionally, in some circumstances, micro tablets can be used in place of granules and pellets. Mini pills offer a safer delivery approach by reducing local irritation and dose dumping. Since they may pass through the duodenum without relying on gastric emptying or intestinal motility, they are particularly beneficial for drugs that are better absorbed in the tiny intestine. In comparison to single-unit bioadhesive tablets, bioadhesive mini tablets exhibit improved adherence and efficacy. Mini tablets are suited for both pediatric and geriatric patients in substitution of pellets and granules. Overall, even though tiny pills have many benefits, it is important to take manufacturing issues and medical needs into account when utilizing this dose form.
CONFLICT OF INTEREST:
The authors have no conflicts of interest regarding this article.
ACKNOWLEDGMENTS:
The authors would like to thank Malla Reddy College of Pharmacy for its extended support towards the authors.
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Received on 02.09.2023 Modified on 14.03.2024
Accepted on 05.07.2024 ©Asian Pharma Press All Right Reserved
Asian J. Res. Pharm. Sci. 2024; 14(3):287-298.
DOI: 10.52711/2231-5659.2024.00047