Multiparticulate Drug Delivery System Research Articles

Polyelectrolyte Complex-based Multiparticulate Drug Delivery System: A Special Emphasis on Chitosan and Alginate

Polyelectrolyte Complex-based Multiparticulate Drug Delivery System: A Special Emphasis on Chitosan and Alginate

Microspheress Types Preparation Evaluation and Applications: A Review

Abstract: Microspheres, also known as microspheres or “monolithic spheres” are small spherical particles that usually range from 1 to 1000 micrometres (µm). This multi-particulate drug delivery system is used in order to obtain controlled and prolonged drug delivery, thus improving the stability, bioavailability, and site specificity at a desired and predetermined rate. There are various methods in order to prepare/formulate the microspheres, such as emulsion-solvent evaporation, extraction of solvent, spray drying, Coacervation, Electrostatic or Electrodynamic, Template or Moulding methods and various other methods that include Thermally Induced Phase Separation (TIPS) and Supercritical Fluid Extraction of Emulsions (SFEE). Every method has its own benefits and disadvantages therefore, the selection of appropriate method is critical in achieving the desired microsphere characteristic. This review covers the different methods used to prepare the microspheres, the variety of parameters used in order to evaluate their effectiveness and their applications in the field of pharmacy.

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.

Preparation and Evaluation of Sustained Release Microbeads Containing Ibuprofen

The current study was carried out in order to prepare sustain release multiparticulate drug delivery system of Ibuprofen which is also known as 2-(4-isobutylphenyl) propionic acid. From the drug excipient study it was found that the drug and polymer were compatible with each other and there was no disappearance, new formation of peaks on the FTIR study. From the DSC study it was seen that there was no change in the melting point of drug when mixed with the polymers. The method applied was Ionotropic gelation. The Microbeads were prepared by employing sodium alginate as a coating agent with HPMC as release retardant and calcium chloride as a cross linking agent. The prepared microbeads were evaluated for various parameters such as micromertics, loose surface crystal study, percentage yield, percent cumulative drug release and surface morphology. From the various evaluated parameters it was revealed that the prepared microbeads were having a good flow property. The percentage yield was found to be in the range of 65.23% - 79.45%, the drug release was found to be in the range of 4.96% - 96.08%. The batch of B7 was the optimized one as it contain higher amount of drug content and shows better amount of drug release then the other batches. The surface morphology study revealed that the optimized formulation was having small cracks or fractures on the surface. From the study we can conclude that this method can be employed for preparing microbeads of Ibuprofen without any difficulty and this formulation can utilized for reducing the dose frequency of Ibuprofen which will not hinder the GIT.

A Review on Floating Multi-particulate Drug Delivery System

The objective of writing this review on Floating Drug Delivery Systems (FDDS) was to accumulate new work with a special focus on the primary floatation mechanism for gastric retention. Drug delivery systems are those that instantly float on contact with gastric fluids and present promising approaches to improve the bioavailability of drugs with absorption windows in the stomach or upper small intestine, imbalanced in the intestinal or colonic environment, and exhibit low solubility at high pH standards. It is a novel drug delivery system that takes full advantage of effectiveness and compliance. Physical problems such as short gastric residence time and unpredictable gastric emptying time were overcome with the use of floating dosage forms that provide the possibility of local and systemic effects. The floating drug delivery system allows prolonged and continuous entry of the drug into the upper part of the gastric retention pathway and increases the bioavailability of the medication characterized by a narrow absorption window. This review provides detailed information on the pharmaceutical basis of its Introduction, Advantages, Disadvantages, Factors Affecting Gastric Emptying, and Criteria for Suitable Drug Products for Floating Gastric-Retention, Classification of Floating Multiparticulate Drug Delivery System, and Characterization of Floating Multiparticulate Drug Delivery System. These systems are beneficial for various difficulties encountered during the development of a pharmaceutical dosage form and the future potential of FDDS. This review article has attempted to announce to readers about the floating drug delivery system.

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.

Demonstration of Advanced Data Mining Tools for Optimization of Pellets Employing Modified Extrusion-pelletization Technique

Background: The multi particulate drug delivery system is preferred due to its numerous advantages but the batch to batch consistency and to achieve desired physical properties are the major challenges in the formulation of such dosage form. Objective: The objective of the present study was to explore the concept of quality by design for the development of galantamine HBr controlled release pellets using a modified palletization technique. Methods: Compritol 888 and Ethocel were chosen as hydrophobic release retardants, while Avicel was chosen as pelletization aid. A compatibility study was conducted between the drug and excipients. Drug loaded extrudes were prepared by using a mixture of isopropyl alcohol, and dichloromethane. Before converting the wet extrudes into pellets, pregelatinized starch was sprinkled on them to improve the physical properties of the pellets. The pellets were characterized for size, shape, and flow. The critical evaluation parameter was the drug dissolution pattern in distilled water. The dissolution data were treated with advanced data mining techniques. The in-vivo profile was predicted employing pharmacokinetic parameters of the drug and in-vitro drug release data of optimized batch pellets. Results: The failure mode and effect analysis revealed that the amount of Compritol 888 ATO and Ethocel were the most critical formulation parameters. The results of FTIR and DSC revealed compatibility between the drug and the excipients. The spherical pellets exhibited good flow. The drug dissolution studies of the batches, prepared according to the central composite design, revealed modified drug release. Multiple regression analysis and analysis of variance were performed to identify statistically significant factors. Contour plots demonstrated the impact of the amount of Compritol 888 and ethyl cellulose. The Design-Expert software was used to identify optimized formulation. The predicted in-vivo plasma concentration-time profile revealed the modified drug release up to 12h. Conclusions: Compritol and Ethocel were able to retard the drug release up to 12 hrs in distilled water. The innovative finding of this study is the use of a dry binder (pregelatinized starch) to improve the characteristics of pellets. Other dry binders are expected to show a similar effect. The newer processing technique can be of use in the industry.

Formulation and In-Vitro Evaluation of immediate-release pellets of Candesartan Cilexetil

Multi particulate drug delivery system has long run also been made use of to enhance the overall bioavailability going from drugs having low aqueous solubility. Candesartan Cilexetil is an anti-hypertensive drug. Complex and dispersion of Candesartan Cilexetil with the different carriers were prepared to increase its solubility and bioavailability. Due to its low aqueous solubility bioavailability of the drug is 15 % and it shows variable absorption from GIT. Pellets offer several advantages such as proper distribution in the GIT tract, reduces dose dumping, and relief going from administration as well as closing going from chemotherapy therefore within the time being work an immediate-release Pellets of candesartan cilexetil was planned out using the representational of increasing the solubility and in turn bioavailability of Candesartan Cilexetil. Immediate release Pellets containing complex or dispersion of Candesartan Cilexetil with the suitable carrier was prepared using non-pareil sugar seeds. On the non-pareil seeds, drug layering of Candesartan Cilexetil complexed or dispersed with the suitable carrier was done. The formulation having Candesartan Cilexetil and Eudragit dispersed in 1:3 ratios is considered the best product concerning assay and in-vitro drug release. The present top of the line used to be promote withstand constancy written report, the results of and that indicated no important change concerning assay, content uniformity, and in vitro drug release.

DRUG DELIVERY STRATEGIES FOR HELICOBACTER PYLORI INFECTION MANAGEMENT: AN OVERVIEW

Helicobacter pylori, profoundly termed as H. pylori, is a gram negative microorganism and a main causative pathogen for gastritis, peptic ulcers, duodenal ulcers and mucosa associated lymphatic tissue (MALt) lymphoma that leads to gastric cancer in infected patients, if uncontrolled in the stipulated time. Until 1994, half of the total world population was suffering from H. pylori infection. based on a WHO survey it is predicted that by 2020, H. pylori infection will be the top ten of the leading causes of death worldwide. this current scenario indicates that it is high time for pathologists, pharmacologists and pharmaceutical formulation development scientists to come together to address the challenge of managing H. pylori infection. this article briefly highlights symptoms, diagnostic tests and various treatment regimens reported for the management of the H. pylori infection. the present article mainly focuses upon novel drug delivery systems developed in the last decade, with special emphasis on the need of gastro retentive drug delivery systems (GRDDS), for effective management of H. pylori infection. targeted drug delivery to the stomach mucosal layer is believed to provide a site-specific effect for eradication of H. pylori. the authors have analysed various reported approaches to deliver drugs for the management of H. pylori infection. It is evident that efficacious results can be obtained with a multi-particulate drug delivery system as compared to a conventional single unit dosage form.

Mucoadhesive Multiparticulate Drug Delivery Systems: An Extensive Review of Patents.

Innovations in pharmaceutical research are striving for designing newer drug therapies to eradicate deadly diseases. Strategies for such inventions always flourish with keys and objectives of minimal adverse effects and effective treatment. Recent trends in pharmaceutical technology specify that mucoadhesive drug delivery system is particularly appropriate than oral control release, for getting local systematic delivery of drugs in GIT for an extended interval of time at a predetermined rate. However, it is somehow expensive and unpleasant sensation for some patients, but still it is needful for getting short enzymatic activity, simple administration without pain and evasion of fast pass metabolism. Usually the vehicles employed in drug delivery of mucoadhesive system have a significant impact that draws further attention to potential benefits like improved bioavailability of therapeutic agents, extensive drug residence time at the site of administration and a comparatively faster drug uptake into the systemic circulation. The drug release from mucoadhesive multiparticulates is contingent on several types of factors comprising carrier need to produce the multiparticles and quantity of medication drug contained in them. Mucoadhesion is characterized by selected theories and mechanisms. Various strategies emergent in mucoadhesive multiparticulate drug delivery system (MMDDS) by in-vitro as well as ex-vivo description and characterization are also critically discussed. Apart from these, the primary focus during this review is to highlight current patents, clinical status, and regulatory policy for enhancement of mucoadhesive multi-particulate drug delivery system in the present scenario.

Statistical design and optimization of ketorolac tromethamine gastroretentive multiparticulate delivery system

The aim of the present research is to design and optimize floating multiparticulate drug delivery system of Ketorolac tromethamine (KT) so as to reduce its irritant effect on the gastric mucosa. Extrusion and spheronization process were used to prepare a drug-containing core pellets. A 3 level 2 experimental factor design was used to examine the effect of the amount of Eudragit RS 100, effervescent agent (NaHCO3: HPMC K4M) on floating lag time and drug release in 6 h. Fourier Transform Infra-Red (FTIR) spectrum, physical characterization, particle size distribution analysis, scanning electron microscopy, floating studies and in vitro drug release studies of prepared floating pellets were evaluated. The study reveals the significant effect of the amount of Eudragit RS 100 and NaHCO3: HPMC K4M on floating lag time and drug release. The optimized batch showed floating lag time of 3.2 min and 95.15% average drug release in 6 hours. 80–95% of pellets remained floating for up to 6 h. All the batches showed excellent flow properties having an angle of repose in the range 29.85±0.20 to 21.60±0.50, Carr’s index and Hausner’s ratio in the range of 14.49±0.26% to 7.54±0.32% and 1.08±0.04 to 1.16±0.7 respectively. The sustained release gastroretentive floating pellets of Ketorolac tromethamine were obtained and could be effectively used in the delivery of drug with less irritant effect on the gastric mucosa.

Development and characterization of a multiparticulate drug delivery system containing indomethacin-phospholipid complex to improve dissolution rate

This study aimed to develop and characterize indomethacin-phosphatidylcholine complex (IPC) as a pellet formulation to enhance the oral bioavailability of poorly water-soluble indomethacin as well as potentially minimize its GI irritations. IPC with different ratio of indomethacin-phosphatidylcholine was prepared by the solvent evaporation method, and their physicochemical investigations such as Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed the formation of the complex. NSAIDs bonded to phosphatidylcholine by cation-π interaction. 1:1 M ratio of indomethacin and phosphatidylcholine was selected as the eligible ratio of IPC and then used to prepare pellets via wet extrusion-spheronization technique. The size, shape, mechanical properties, surface morphology and in vitro drug release behavior of pellets were characterized. Pellets were found to be spherical, 500–1180 μm size and had >70% yield. Scanning electron microscopic (SEM) studies confirmed spherical shape and smooth surface of pellets. IPC pellets resulted in an improved dissolution of the drug (released >90%) compared with control formulation (released <50%) at pH 7.4 within 2 h. The results indicated successful incorporation of the indomethacin-phosphatidylcholine complex into pellets with the improved dissolution rate of the drug which may be considered for improved bioavailability of indomethacin.

Development and Optimization of a Floating Multiparticulate Drug Delivery System for Norfloxacin.

Norfloxacin is a synthetic broad-spectrum antibacterial drug having poor bioavailability and pH-dependent solubility. The purpose of the present study was to develop a gastroretentive floating multiparticulate drug delivery system for norfloxacin. Norfloxacin core pellets were prepared using microcrystalline cellulose (MCC) and polyvinylpyrrolidone K30 (PVP K30) by extrusion and spheronization. A 3-level, 3-factor, 17-run experimental Box-Behnken design was adopted to optimize levels of variables in the pellets' formulations. The selected independent variables were amounts of MCC and PVP K30 and spheronizing speed and the dependent variables were aspect ratio and hardness of pellets. Sodium bicarbonate and hydroxypropyl methylcellulose K15M in the ratios of 1:1, 1:2, and 2:1 (w/w) on a dry solid basis were incorporated into the norfloxacin pellets and they were further coated with Eudragit RL 100 using a fluidized bed processor to obtain weight gain of 5%, 10%, and 15% w/w. The fourier transform infrared spectrum, scanning electron microscopy, physical characterization, particle size distribution analysis, floating studies, and in vitro drug release studies of the pellets were evaluated. Among the floating multiparticulate pellets batches, batch B-22 was found to be optimized based on the criteria of attaining the minimum floating lag time (<10 min) and the maximum value of drug released 82.11% in 8 h. The percentage drug release for batches B-21 and B-23 was 91.12% in 5 h and 60.67% in 8 h, respectively. The drug release studies indicated that as the Eudragit RL 100 polymer coat increases the drug release decreases, producing sustained release of norfloxacin. The floating studies revealed that 70%-90% of pellets remained floating for up to 8 h. All the batches have excellent flow properties with angle of repose in the range of 25.5±0.49° to 28.02±0.30°, and Carr's index and Hausner's ratio in the range of 5% to 15% and 1.05±0.3 to 1.14±0.3, respectively. The significant outcome obtained in the study is that such an approach can be effectively employed for improvement of the bioavailability of drugs having poor absorption in the lower part of the gastrointestinal tract with enhanced therapeutic efficacy.

Formulation and Evaluation of Multi-particulate Drug Delivery System for Metformin Hydrochloride by Spray Drying Method

Formulation and Evaluation of Multi-particulate Drug Delivery System for Metformin Hydrochloride by Spray Drying Method

Chitosan phthalate: A novel polymer for the multiparticulate drug delivery system for diclofenac sodium

AbstractThis study investigates the preparation of colon specific drug delivery of diclofenac sodium (DS) using maltiparticulate system with chitosan phthalate (CP). Technique adopted to prepare sphere shaped multiparticulate system was extrusion and spheronization. The prepared pellets resulted with good spherical geometry with 1.1 ± 0.20 mm diameter. DS loaded system shows a maximum delivery pH of 7.4 and the same depressed at pH 1.2. The developed system significantly (p &lt; .05) increase in the peak plasma concentration (Cmax) of DS pellets when compared to that of pure DS. As expected the novel formulation showed a significant increase in oral bioavailability of DS for about three times. Additionally, the CP pellets of DS showed a momentous improvement in anti‐inflammatory activity and reduced/ inhibited ulcer index.

Development and In vitro-In vivo Characterization of Chronomodulated Multi-Particulate Drug Delivery System of Terbutaline Sulphate for Treatment of Nocturnal Asthma by box–Behnken Statistical Design

Pulsatile Drug Delivery System: an Approach of Medication according to Circadian RhythmAnamika Singh, Harikesh Dubey, Indu Shukla,Dharmchand. P. Singh

Formulation and Optimization of Multiparticulate Drug Delivery System Approach for High Drug Loading.

The aim of the present work was to develop and optimize multiparticulate formulation viz. pellets of naproxen by employing QbD and risk assessment approach. Mixture design with extreme vertices was applied to the formulation with high loading of drug (about 90%) and extrusion-spheronization as a process for manufacturing pellets. Independent variables chosen were level of microcrystalline cellulose (MCC)-X 1, polyvinylpyrrolidone K-90 (PVP K-90)-X 2, croscarmellose sodium (CCS)-X 3, and polacrilin potassium (PP)-X 4. Dependent variables considered were disintegration time (DT)-Y 1, sphericity-Y 2, and percent drug release-Y 3. The formulation was optimized based on the batches generated by MiniTab 17 software. The batch with maximum composite desirability (0.98) proved to be optimum. From the evaluation of design batches, it was observed that, even in low variation, the excipients affect the pelletization property of the blend and also the final drug release. In conclusion, pellets with high drug loading can be effectively manufactured and optimized systematically using QbD approach.

Design and evaluation of an innovative floating and bioadhesive multiparticulate drug delivery system based on hollow structure

In this study a gastric-retentive delivery system was prepared by a novel method which is reported here for the first time. An innovative floating and bioadhesive drug delivery system with a hollow structure was designed and prepared. The floating and bioadhesive drug delivery system was composed of a hollow spherical shell, a waterproof layer (Stearic acid), a drug layer (Ofloxacin), a release retarding film (the novel blended coating materials) and a bioadhesive layer (Carbomer 934P) prepared by using a liquid multi-layering process. A novel blended coating material was designed and investigated to solve the problem of the initial burst release of the formulation and the release mechanism of the novel material was analyzed in this study. The optimized formulation provided the sustained release characteristic and was able to float for 24h. The SEM cross-section images showed that the particulates were hollow with a spherical shell. X-ray images and pharmacokinetic studies (Frel=124.1±28.9%) in vivo showed that the gastric-retentive delivery system can be retained in the stomach for more than 6h. The floating and bioadhesive particulate drug delivery system based on a hollow structure with a dual function presented here is a viable alternative to other for gastroretentive drug delivery system.

A Review on Long Acting PLGA Based in Situ Forming Microparticles Formulation for a Novel Drug Delivery System

Pharmaceutical research has recently been focusing on new inject able drug delivery systems which provide long therapeutic effects, minimum initial burst effect, reduced side effects, and involving simplified production stages and facilitate application process. In situ forming micro particle (ISM) systems, one of the latest approaches in this field, offer a new encapsulation technique and meet the objectives state above. Factors such as the carrier use to form the multiparticles, amount and type of drug and the vehicle type can be taken as the main performance criteria for these systems. Ongoing studies have shown that this new multiparticulate drug delivery system is suitable for achieving new implant delivery system with low risk of dose-dumping, capable of being modulated to exhibit varying release patterns, reproducible, easily applicable and well-tolerable. A novel in situ method for the preparation of inject able biodegradable poly(lactide-co-glycolide) (PLGA) micro particle for the controlled delivery of drug using DMSO as solvent. A stable dispersion of PLGA microglobules (‘premicroparticles’ or ‘embryonic micro particles’) in a vehicle mixture usually biocompatible oils on injection comes in contact with water from aqueous buffer or physiological fluid, thereby hardening the microglobules into solid matrix type micro particles entrapping the drug (in situ forming micro particles). The myotoxicity was assessed by measuring the cumulative release of creatine kinase (CK) to evaluate the muscle damage caused by this formulation. CK release will be significant lower decreased with a lower polymer phase: oil phase ratio. The vivo studies confirmed the in vitro data and showed good muscle compatibility of the ISM-system.

Design and Development of Multi Particulate System for Targeted Drug Delivery Using Natural Polymer

Okra mucilage has been used to reduce the cholesterol level since microspheres has formulated by using okra mucilage to develop a synergistic effect. Biodegradable and biocompatible okra (Abelmoschus esculentus) mucilage was extracted for the development of controlled release multi-particulate drug delivery system. Surface morphological characteristics were studied using scanning electron microscopy. Concentrated solution containing different proportion of natural materials i.e. okra mucilage and sodium alginate were used to formulate the microspheres in the calcium chloride solution. Calcium chloride act as a cross linking agent, when react with sodium alginate form a calcium alginate, since developed a gel like microspheres. The formulated microspheres were thereafter loaded with losartan potassium. These formulations were evaluated by different parameters like percentage yield, particle size, particle shape, surface morphology and in vitro release properties etc. Approximately nine formulations were studied in which F6 formulation has shown a major differentiating factor as per study. High % yield in F7 formulation was found to be 99.01%. All the formulations showed good swelling characteristics in simulated intestinal fluid (pH 7.4). During study of drug release, the rate and extent of drug release decreased significantly with increase of concentration of polymer and calcium chloride, release data shows that F6 formulation has shown a major differentiating factor given the best result of drug release which was found to be 91.50% after 6 hr in simulated intestinal fluid (pH 7.4). The prepared microspheres show controlled release effect of losartan potassium. The study has revealed that natural materials can be used for formulation of controlled release microspheres and will provide more opportunities for further study.