Multiparticulate Drug Delivery Systems Research Articles

Prilling of crystallizable water-in-oil emulsions: Towards co-encapsulation of hydrophilic and lipophilic active ingredients within lipid microparticles.

Multiparticulate drug delivery systems offer advantages in controlled release, dose flexibility, and personalized medicine. Fusion prilling, a process that produces spherical lipid-based microparticles through vibrating nozzles, is gaining interest in the field. This study aims to explore the use of fusion prilling to encapsulate crystallizable water-in-oil emulsions, enabling the incorporation of hydrophilic active pharmaceutical ingredients (APIs) within lipid matrices. Urea (highly water-soluble) and Erythromycin (poorly water-soluble) were selected as model compounds, solubilized in the aqueous and lipid phases, respectively. The first phase of the study evaluated lipid excipients for their suitability in prilling, ensuring microparticle consistency in shape, size, and stability. The second phase focused on characterizing microparticles notably in terms of structural organization and integrity. Results demonstrated successful encapsulation of both model compounds, with high efficiency, by omitting an additional emulsification step. Despite concerns over water evaporation during processing, microparticles remained stable for up to 14 months when stored at room temperature in a hermetically sealed container. This work highlights the potential of fusion prilling for multiparticulate drug delivery systems, even for formulating APIs with different solubility profiles. Future research should focus on optimizing the process for broader API incorporation.

A Panoramic Review on Microparticles

Microparticles, microspheres, and microcapsules are common multiparticulate drug delivery systems with technological and medical benefits. Microparticles are employed extensively these days. In order to improve efficacy, tolerance, and patient compliance, microparticles are used as multi-unit drug delivery systems with clearly defined physiological and pharmacokinetic benefits. The size of their particles varies from 0.1 to 1000 μm. A range of polymers have been employed in the synthesis of microparticles for drug delivery research in an effort to boost therapeutic efficacy while reducing negative effects. These days, glass, ceramic, and polymers are used to create microparticles. This method is used to deliver medications to particular regions. Microparticles are also used for regulated, prolonged, and long-term release. to treat a variety of illnesses, including inflammation, cancer, heart disease, ocular disorders, and psychotic disorders. This review covers the pros, cons, type of microparticles, preparation method, evaluation of microparticles and applications.

Exploring the potential of carbocisteine loaded microparticulate system by using ccd model for the treatment of respiratory infections

Background: Multi-particulate drug delivery systems (microbeads) deliver drugs over an extended period, distributing them evenly throughout the gastrointestinal tract and minimizing local irritation. Microbeads are small, solid, free-flowing particulate carriers that contain drug particles that have been dispersed and are either crystalline in solution. Aim: The present work explores the potential of the carbocisteine-loaded floating microparticulate drug delivery system. Methodology: Floating microbeads were prepared using the ionotropic gelation method and optimized using Central Composite Design. Result and discussion: Floating microbeads of prepared carbocisteine were evaluated for the FTIR study, which reveals no interaction between the drug and other excipients. Buoyancy time, drug content, particle size, and % drug release were also characterized; it found that drug release was 90.24 %, up to 17 hours, 250 to 220 µm, and drug content 96.67%, respectively, for the optimized batch. An accelerated stability study was performed, showing that the formulation was stable. Floating microparticulate drugs were prepared, and batch B-3 was optimized based on in-vitro buoyancy and release patterns. The floating ability of the beads was observed visually for 10 to 17 hr, and an increase in polymer concentration decreased the swelling of the beads. Conclusion: The results obtained from the formulation batch B-3 show good results for all the parameters tested. Floating microbeads could be the best possible approach to deliver drugs with the benefit of reduced dosing frequency

Multiparticulate Drug Delivery of Losartan Potassium via Extrusion-Spheronization: Formulation and Dissolution Comparisons

Abstract Background: Losartan potassium, an antihypertensive medication, has high solubility and a short half-life that result in potential adverse effects and rapid drug clearance. Multiparticulate drug delivery systems enhance the drug’s bioavailability, decrease patient-to-patient variability, and optimize drug distribution. Herein, losartan potassium pellets for sustained drug release were developed and characterized. Methods: The formulation process involved varying the concentrations of Eudragit RSPO (200 mg, 400 mg, or 600 mg) and Eudragit L100 (200 mg, 400 mg, or 600 mg) across nine pellet batches, and adjusting the triethyl citrate concentrations accordingly. The pellets’ bulk density, tapped density, flow properties (Carr’s index, Hausner’s ratio, and angle of repose), drug content, particle size distribution, and in vitro drug release were evaluated. Interactions between losartan potassium and the excipients were analyzed with FTIR and DSC. Results: FTIR spectra indicated physical interactions without major chemical alterations, whereas DSC thermograms revealed changes in thermal behavior due to excipient interactions. In vitro drug release studies indicated that formulations with higher concentrations of Eudragit RSPO and triethyl citrate achieved controlled, prolonged drug release. The optimized batch (F7) demonstrated balanced characteristics including favorable bulk and tapped density, good flow properties, and a sustained release profile. Varying the polymer and plasticizer concentrations significantly influenced pellet performance, and F7 was found to be the most promising formulation for sustained-release applications. Conclusion: This study underscores the importance of polymer selection and formulation optimization in developing effective sustained-release drug delivery systems, and has potential implications for enhancing therapeutic outcomes in clinical practice.

Comparison of Mini-Tablets and Pellets as Multiparticulate Drug Delivery Systems for Controlled Drug Release

Mini-tablets made into hard capsules or administered using special dosing units, as well as pellets in hard capsules or compressed into tablets, offer the advantages of multiparticulate drug delivery systems and are suitable for controlled drug release using polymer coatings. Four different kinds of solid drug preparations were manufactured and investigated concerning drug release. Inert pellets were coated with the model drug sodium benzoate and, in a second step, with the insoluble polymer ethylcellulose. The coated pellets were compressed into mini-tablets and into normal tablets. Another kind of mini-tablet was compressed from a sodium benzoate compression mixture and finally coated with ethylcellulose. The coating of the tablets was performed using fluidized bed technology. The sodium benzoate release plots of the coated pellets show a lag time and retarded release according first-order kinetics. The mini-tablets and normal tablets compressed from pellets release sodium benzoate according to first-order kinetics as well, but without the lag time due to distinct ethylcellulose layer destruction during tableting. The release is retarded with increasing ethylcellulose layer thickness on directly compressed mini-tablets. The different formulations of coated pellets, mini-tablets, and normal tablets offer a broad choice for variable drug release kinetics depending on the biopharmaceutical and pharmacological requirements.

Microspheres in Pharmaceutical Science

Microcapsules are multi-particulate drug-delivery systems that can be configured to accomplish extended or controlled drug delivery to improve bioavailability, balance, and to target the medication to a specific webpage online at a set rate. They are made of polymers that are natural, semi-natural, and artificial, as well as polymeric wax or other shielding substances. Usually made of free-flowing powders with protein or synthetic polymer particles, microspheres have sizes between 1 to 1000 micrometer. The range of microsphere training approaches offers multiple ways to manipulate them as drug management components and to enhance the therapeutic potency of a particular medicine. In comparison to normal dose forms, these transport structures offer various advantages, including increased efficacy and decreased toxicity. Stepped forward affected person compliance and convenience.

A review on natural polymer-based microsphere

Microspheres having free flowing powder characteristics, which are consisting of synthetic polymers and proteins. These are biodegradable in nature having particle size less than 200um. Microspheres are the multiparticulate drug delivery systems which are consisting from natural and synthetic material. Microspheres received much attention not only for prolonged release, but also for targeting of anticancer drugs. In future by combining various other strategies, microspheres will find the central place in novel drug delivery, particularly in diseased cell sorting, diagnostics, gene & genetic materials, safe, targeted and effective in vivo delivery and supplements as miniature versions of diseased organ and tissues in the body.

Development of a multiparticulate drug delivery system for in situ amorphisation

In the current study, the concept of multiparticulate drug delivery systems (MDDS) was applied to tablets intended for the amorphisation of supersaturated granular ASDs in situ, i.e. amorphisation within the final dosage form by microwave irradiation. The MDDS concept was hypothesised to ensure geometric and structural stability of the dosage form and to improve the in vitro disintegration and dissolution characteristics. Granules were prepared in two sizes (small and large) containing the crystalline drug celecoxib (CCX) and polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA) at a 50 % w/w drug load as well as sodium dihydrogen phosphate monohydrate as the microwave absorbing excipient. The granules were subsequently embedded in an extra-granular tablet phase composed of either the filler microcrystalline cellulose (MCC) or mannitol (MAN), as well as the disintegrant crospovidone and the lubricant magnesium stearate. The tensile strength and disintegration time were investigated prior to and after 10 min of microwave irradiation (800 and 1000 W) and the formed ASDs were characterised by X-ray powder diffraction and modulated differential scanning calorimetry. Additionally, the internal structure was elucidated by X-ray micro-Computed Tomography (XµCT) and, finally, the dissolution performance of selected tablets was investigated. The MDDS tablets displayed no geometrical changes after microwave irradiation, however, the tensile strength and disintegration time generally increased. Complete amorphisation of CCX was achieved only for the MCC-based tablets at a power input of 1000 W, while MAN-based tablets displayed partial amorphisation independent of power input. The complete amorphisation of CCX was associated with the fusion of individual ASD granules within the tablets, which negatively impacted the subsequent disintegration and dissolution performance. For these tablets, supersaturation was only observed after 60 min. On the other hand, the partially amorphised MDDS tablets displayed complete disintegration during the dissolution experiments, resulting in a fast onset of supersaturation within 5 min and an approx. 3.5-fold degree of supersaturation within the experimental timeframe (3 h). Overall, the MDDS concept was shown to potentially be a feasible dosage form for in situ amorphisation, however, there is still room for improvement to obtain a both fully amorphous and disintegrating system.

An overview on fundamentals of immediate release drug delivery system

Tablet is most popular among all dosage forms today because of its convenience, ease of administration, greater flexibility in dosage form design, ease of production, and low cost and non-invasive therapy. Formulation of tablets requires API along with excipients. Excipients include lubricants, diluents, binders, glidants, disintegrants, sweetening agents, flavoring agents, etc. Recent trends indicate that multi-particulate drug delivery systems are suitable for achieving extended-release oral formulation with a low risk of dose dumping, mixing flexibility to attain difference release patterns, and reproducible and short gastric residence time. Modern technology in immediate-release tablets, such as novel granulation techniques and electrostatic dry powder coating techniques, are prevalent nowadays. Recently, the immediate-release formulation has been similar to various sustained-release formulations that are currently readily attainable.

Review: Oral Beads as a Platform for Sustained Drug Delivery

Multiparticulate drug delivery systems extend the frontier of pharmaceutical progress future by offering marvellous prospects for designing unique controlled and delayed-release oral preparations. Beads are composed of many distinct units. The preparation of microbeads drug delivery system is one of the alternatives which include neither utilization of harsh chemical nor raised temperature. This presented review gives a special emphasis on beads technology, ionic gelation and modified methodologies for preparation of beads. In general, the ionic gelation method mainly relies on the cross-linking between polyelectrolytes counterions and eventually, hydrogels will be formed. Natural origin polysaccharides biopolymers utilization has been widely augmented especially in controlled \ sustained formulation; accordingly, an eco-friendly pharmaceutical product can be provided. Furthermore, the review shed light on merits, limitations, promising polymers involved in the preparation, recent advances of multiple-unit drug delivery system approach based on Ionotropic gelation method, pharmaceutical application, and several basic evaluation characteristics.

Different evaluation parameters of floating microsphere of ofloxacin

The Floating Microsphere of Ofloxacin requires a novel gastroretentive drug delivery system which can provide an extended period of time in stomach and improve oral bioavailability. Floating microspheres were characterized for floating ability, compatibility study, particle size and shape, entrapment efficiency, in-vitro drug release. Due to their low density, these multi particulate drug delivery systems showed good floating ability and remained in gastric environment for more than 24 hrs, required for sustained therapeutic activity. Major advantages of the system include ease of preparation, good floating ability, high encapsulation efficiency and sustained drug release over 24 hours. From this study, it was concluded that formulation of floating microspheres of ofloxacin offers prolonged gastric residence time and continuous release of the medication over an extended period of time thus oral bioavailability of the drug and subsequent efficacy is improved.

A Novel Drug Delivery of Microspheres

Microspheres are multiparticulate drug delivery systems that distribute medications at a predetermined rate to a specific region. Microspheres are free-flowing powders manufactured from biodegradable proteins or synthetic polymers, with particle sizes ranging from 1 to 1000 micrometers. Benefits of using microspheres in medication delivery, bone tissue manufacture, and pollutant absorption and desorption by regeneration .The study demonstrates how microsphere parameters are planned and measured. Bioadhesive microspheres, polymeric microspheres, magnetic microspheres, floating microspheres, and radioactive microspheres are only a few examples of complicated microspheres. Cosmetics, oral medication administration, target drug delivery, ocular drug delivery, gene delivery, and other industries covered in the paper could all benefit from microspheres. To ensure best therapeutic effectiveness, the agent must be delivered to target tissue at an optimal amount during the appropriate timeframe, with low toxicity and adverse effects. There are several methods for delivering the therapeutic substance to the target site in a controlled manner. The use of microspheres as medication carriers is one such technique. The value of microspheres as a novel drug delivery carrier to accomplish site-specific drug delivery was discussed in this article.
 Keywords: Microspheres, method of preparations, polymer bioadhesion, types of microspheres.

Microspheres as Therapeutically effective Multiparticulate Drug Delivery System: A Systemic Review

Therapeutic research and development are increasingly focusing on delivery systems which enhance desirable objectives while minimizing side effects. Nowadays Dose dumping is a major problem of single particulate dosage forms. So there is a need of extended release Multi-particulate drug delivery systems. Microspheres are multiparticulate drug delivery systems which are prepared to obtain prolonged or controlled drug delivery to improve bioavailability, stability and to target the drug to specific site at a predetermined rate. In strict sense, they are spherical empty particles. The pharmaceutical scientists have achieved a great success in developing most therapeutic systems with suitable natural polymer. Multi-particulate drug delivery systems are developed to address the challenges of drug development. A well designed drug delivery system can overcome some of the problems of conventional therapy and enhance the therapeutic efficacy of given drug. It is the reliable means to deliver the drug to the target site specifically. They received much attention for prolonged release as well as targeting to treat various diseases. This Current review outlines the transient account of classification, methods of preparations, its application and also the evaluation characterization for their efficiency of microspheres.

Improved efficacy and safety of low doses of benznidazole-loaded multiparticulate delivery systems in experimental Chagas disease therapy

Benznidazole (BZ) is a first-line drug for the treatment of Chagas disease; however, it presents several disadvantages that could hamper its therapeutic success. Multiparticulate drug delivery systems (MDDS) are promising carriers to improve the performance of drugs. We developed BZ-loaded MDDS intended for improving Chagas disease therapy. To assess their efficacy and safety, Trypanosoma (T) cruzi infected BALB/c mice were orally treated with free BZ or BZ-MDDS at different regimens (doses of 50 and 100 mg/kg/day, administered daily or at 2- or 5-days intervals) and compared with infected non-treated (INT) mice. At 100 mg/kg/day, independent of the administration regimen, both treatments were able to override the parasitemia, and at 50 mg/kg/day significantly reduced it compared to INT mice. BZ-MDDS at a dose of 100 mg/kg/day administered every 5 days (BZ-MDDS 100–13d) induced the lowest cardiac parasite load, indicating an improved efficacy with lower total dose of BZ when loaded to the MDDS. Reactive oxygen species produced by leukocytes were higher in INT and mice treated with BZ at 50 mg/kg/day compared to 100 mg/kg/day, likely because of persistent infection. BZ-MDDS treatments markedly reduced heart and liver injury markers compared to INT mice and those receiving the standard treatment. Therefore, BZ-MDDS exhibited enhanced activity against T. cruzi infection even at lower doses and reduced administration frequency compared to free BZ while increasing the treatment safety. They likely avoid undesired side effects of BZ by keeping a sustained concentration, avoiding plasmatic drug peaks. BZ-MDDS evidenced significant improvements in experimental Chagas disease treatment and can be considered as a potential improved therapeutic alternative against this illness.

A Novel Drug Delivery System: Review on Microspheres

Microspheres are multiparticulate drug delivery systems that are designed to deliver drugs to a particular location at a fixed rate. Microspheres are free-flowing powders made up of biodegradable proteins or synthetic polymers with particle sizes ranging from 1 to 1000µm. Benefits of the use of microspheres in fields such as drug delivery, bone tissue manufacturing, and the absorption and desorption of contaminants by regeneration. The study shows the method of planning and measurement of microsphere parameters. Microspheres are complex, such as bioadhesive microspheres, polymeric microspheres, magnetic microspheres, floating microspheres, radioactive microspheres. Microspheres may be used in various fields such as cosmetics, oral drug delivery, target drug delivery, ophthalmic drug delivery, gene delivery, and others listed in the study. In order to achieve optimal therapeutic effectiveness, it is important to deliver the agent to the target tissue at an optimum level within the right timeframe, resulting in little toxicity and minimal side effects. There are different approaches to supplying the medicinal drug to the target site in a continuous managed manner. One such strategy is the use of microspheres as drug carriers. In this article, the value of the microsphere is seen as a novel drug delivery carrier to achieve site-specific drug delivery was discussed.
 Keywords: microspheres, method of preparations, polymer, bioadhesion, types of microspheres

Multiple Unite Pellet Systems (MUPS) as Drug Delivery model

Multiparticulate drug delivery systems are mainly oral dosage form, consist of small discrete units that exhibit different characteristics especially in release pattern and drug bioavailability. These systems are represented by granules, pellets, microspheres, microcapsules, and minitablets. Pellets offer high flexibility in the design, formulation, and development of oral dosage forms such as sachet, suspension, capsule, and tablet. Multiparticulate tablets manufactured by compaction of multiple unite pellets is one of the latest and, yet, challenging technologies. Multiparticulate tablets combine the benefits of both a tablet and a pellet-filled capsule in one dosage form but their manufacturing experience many difficulties. The oral multiparticulate products consist of polymer-coated subunits or pellets, which are embedded in an inert excipients’ matrix, formulated to overcome the difficulty in administering capsules and improve the physicochemical stability of suspension and offer predictable release and uniform distribution in the gastro-intestinal tract compared to the plain tablet. This review discusses the advantages and drawbacks of MUPS, the properties of an ideal MUPS, various pharmaceutical applications of MUPS, the challenges and key variables that to be considered in the tableting process for successful production of MUPS
 Keywords: MUPS®, Pellets, Multiparticulate tablets.

Mucoadhesive Pellets for Drug Delivery Applications: A Critical Review

Pellets are spherical shaped multiparticulate drug delivery systems with size ranging between 0.5-2.0 mm. Free flow, good mechanical properties, improved physical and chemical properties of powder, and stability are some advantages of pellets. Mucoadhesive pellets could be developed by using appropriate concentration and type of mucoadhesive polymer. Mucoadhesive pellets can be used for delivery of drugs to gastric, colonic, and vaginal regions. Immediate release, sustained/controlled release and implantable delivery could be incorporated using mucoadhesive pellets. Reproducibility, ease of scalability, quality control checks and significant mechanical strength are some advantages making pellets widely acceptable by pharmaceutical industry. In the present review, mucoadhesion process and theories, mucoadhesive polymers, pelletization process, evaluation of pellets and reported research/patents on mucoadhesive pellets for delivery of different categories of drugs have been presented.

Formulation Development and Evaluation of Duloxetine Hydrochloride Multi-Particulate Delayed-Release Capsules

Background: Multi-particulate drug delivery systems are mainly oral dosage forms consisting of a multiplicity of small discrete units, each exhibiting some desired characteristics. Duloxetine hydrochloride is acid-labile thus it is formulated as gastro-resistant pellets. Objective: The work aims to develop Delayed-release oral capsules comprising Duloxetine Hcl pellets which is similar in dissolution profile and bioavailability, there by establishing bio equivalence to that of the reference product-Cymbalta®. Methods: The pellets are formulated in a fluidised bed processor, by Wurster process. The finished pellet consists of four different layers, coated over the sugar spheres. The first layer is the drug layer, followed by a barrier layer to separate enteric layer and drug, finally a top layer that acts as a moisture barrier. The pharmaceutical equivalence and stability of finished product to that of the standard was the primary objective during the development of each layer. Thus, in all stages of development, the dissolution and stability were closely monitored and the excipients were optimized based omit. Results: Poor process efficiency, multi-pellet formation and low dissolution of the drug layer are resolved by the addition of HPMC, talc and corn starch respectively. The moisture permeability across the barrier layer was arrested by Opadry® AMB white. 25-30%. 25% coating thickness with Eudragit L-30-D55 provides acid resistance and timely drug release. Finally, a 5% coating with Opadry® AMB again provides complete moisture protection. Conclusion: Developed pharmaceutically equivalent and stable dosage form of Duloxetine Hydrochloride

Evaluation of Experimental Multi-Particulate Polymer-Coated Drug Delivery Systems with Meloxicam

The objectives of this study are the development and evaluation of modified release multi-particulate drug delivery systems containing a BCS class II drug (meloxicam), formulated as polymer-coated pellets. Inert seeds containing microcrystalline cellulose, lactose monohydrate, and polyvinylpyrrolidone were prepared by extrusion-spheronization. The obtained cores were loaded with meloxicam using the drug layering technique, by spray coating in a fluidized bed with a liquid dispersion of the drug. The resulting drug pellets were film-coated with various polymers (Acryl-EZE® 93O, Eudragit® RS 30-D as well as experimental composite obtained by adding Methocel™ E5 Premium LV as pore forming agent to the extended release polymer Eudragit® RS 30-D). All experimental systems were evaluated by scanning electron microscopy and in vitro release testing, in an attempt to investigate the characteristics of the film coatings and their influence on drug release from the multi-particulate systems. The in vitro release study was performed in two stages, using two media with pH values corresponding to the gastric and intestinal environment (HCl 0.1N, pH = 1.2 for the first two hours of the test and phosphate buffer 50 mM, pH 6.8 for the next 4 h). The in vitro release data have highlighted the impact of the formulation factors on the drug release.

Release of the Non-Steroidal Anti-Inflammatory Drug Flufenamic Acid by Multiparticulate Delivery Systems Promotes Adipogenic Differentiation of Adipose-Derived Stem Cells.

Engineered tissue-like structures often instigate an inflammatory response in the host that can inhibit wound healing and ultimately lead to the rejection of the implant. In our previous study, we have characterized the properties and biocompatibility of novel multiparticulate drug delivery systems (MDDS), based on collagen matrix with gradual release of anti-inflammatory drug flufenamic acid, we evaluated their anti-inflammatory potential and demonstrated their efficiency against burns and soft tissue lesions. In addition to these results, FA was previously described as a stimulant for adipogenesis, therefore we hypothesized that MDDS might also be appropriate for adipose tissue engineering. After the cell-scaffold constructs were obtained, cell morphology, adhesion and spreading on the systems were highlighted by scanning electron microscopy, immunostaining and confocal microscopy. The effect of FA-enriched materials on adipogenesis was evaluated at gene and protein level, by RT-qPCR, confocal microscopy and immunohistochemistry. Our current work indicates that flufenamic acid plays a beneficial role in adipocyte differentiation, with a direct effect upon the gene and protein expression of important early and late markers of adipogenesis, such as PPARγ2 and perilipin.