Modified Release Drug Delivery Systems Research Articles

A Review on Osmotic Drug Delivery System

Conventional drug delivery systems have slight control over their drug release and nearly uncontrollable over the effective concentration at the target site. This type of dosing pattern might effect on constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled design over a prolonged period of time by the controlled or modified release drug delivery systems. For most of the drugs, oral route is the most tolerable route of administration. Certain molecules may have low oral bioavailability because of solubility or permeability limitations. Evolution of an extended-release dosage form also need sensible absorption throughout the gastro-intestinal tract (GIT). Among the existing techniques to improve the bioavailability of these drugs fabrication of osmotic drug delivery system is the most suitable one. Osmotic drug delivery systems release the drug with the zero-order kinetics at a constant rate. This review brings out advantages, disadvantages, principles, basic components and classification of osmotic drug delivery systems.

Effect of Eudragit S 100 polymer on sustained release of sodium diclofenac coated and uncoated microspheres

Diclofenac sodium were taken as a model drug and belongs to NSAIDS. Diclofenac sodium prevents production of prostaglandins and thus exerts its analgesic action and inhibits leukocyte formation to induce anti-inflammatory action. It is tremendously recommended to reduce and overcome signs and symptoms of rheumatoid arthritis, osteo-arthritis andankylosing spondylitis. This present study was to investigate the dissolution profile and release kinetics of modified release diclofenac sodium microspheres containing sodium alginate and Eudragit S-100. Microspheres were prepared by using ionotropic gelation technique and coated by using coacervation phase separation method using different ratios of eudragit S100 which is a pH sensitive polymer. Both coated and uncoated diclofenac sodium microspheres were evaluated for % yield, entrapment efficiency, flow property, in vitro percent drug release. which were spherical in shape, were rough and smooth, respectively. The size of the core microspheres ranged from 450 to 550 μm and the size of the coated microspheres ranged from 500 to 700 μm. The core microspheres sustained the release for 12hrs in a pH progression medium mimicking the condition of GIT. The release studies of coated microspheres were performed in a similar dissolution medium as mentioned above. In acidic medium, the release rate was much slower. However, the drug was released quickly at pH 7.4 and their release was sustained up to 24 hrs. Finally, it was concluded that eudragit L100 and ethyl cellulose were appropriate polymers to prepare microspheres of diclofenac sodium as modified release drug delivery system.

Hydrogels for Modified-release Drug Delivery Systems.

Hydrogels for the modified-release drug delivery systems are a continuously growing area of interest for the pharmaceutical industry. According to the global market, the profit resulting from the use of polymers in this area is projected to reach $31.4 million by 2027. This review discusses the recent advances in and perspectives of hydrogel in drug delivery systems for oral, parenteral, nasal, topical, and ophthalmic delivery. The search was conducted, in January 2021, in an extensive database to identify studies published from January 2010 to December 2020. We described the main characteristic of the polymers to obtain an ideal hydrogel for a specific route of administration and the formulations. It was concluded that the hydrogels are useful to decrease the number of doses and side effects, promote adhesion of patient, and enhance the bioavailability of the drugs, thus improving the safety and efficacy of the treatment.

Hydrogels for Modified-release Drug Delivery Systems

Hydrogels for Modified-release Drug Delivery Systems

Effect of the compaction parameters on the final structure and properties of a press-coated tablet (Tab-in-Tab): Experimental and numerical study of the influence of core and shell dimensions

With increasing interest in chronopharmaceutics, press-coated tablets have become a key technology in the field of modified release drug delivery systems. Although their benefits in terms of drug release have been largely studied, the comprehension of the compaction process of press-coated tablets is yet to complete. Particularly, the effects of geometrical parameters like the ratios between the thickness/diameter of the core and the thickness/diameter of the whole tablet were so far not much considered. Moreover, there is only few studies in the literature about the effect of the press-coating compression on the final structure and properties of the core. The present work consists in a joint experimental and numerical study that aims to assess these points. The study revealed high stress concentrations on the core during compression, causing high permanent deformations of the core, especially when the ratio between the core thickness and the total tablet thickness was high. The mechanical properties of the core tablet were also shown to be impacted: its density and strength were found to decrease before increasing again along the coating-compression. This effect was highlighted to be dependent on the triaxiality of the stress state (i.e. the ratio between the stresses in the different directions), itself depending on the two studied geometrical parameters. As the properties of the core affect the release attributes, ratios between the dimensions of the core and the dimensions of the whole tablet (thickness, diameter) should be taken into account as critical parameters for the manufacture of press-coated tablets.

A review on applications of Hydroxy propyl methyl cellulose and natural polymers for the development of modified release drug delivery systems

A review on applications of Hydroxy propyl methyl cellulose and natural polymers for the development of modified release drug delivery systems

Formulation Optimization of Polyox Based Modified Release Drug Delivery System

Polyethylene Oxide (PEOs) offer specific advantages to be used in pharmaceutical products as release modifiers by forming a hydrogel around the dosage form in aqueous environment causing the drug to follow a diffusional path before releasing into the media. The strength of the hydrogel governs the release retardation capacity of the PEO system. The objective of this dissertation work was to use the Design of Experiments methodology to develop and optimize a PEO based modified release formulation of a highly water-soluble drug like Metoprolol succinate. The effect of the different viscosity grade PEOs, their concentration with respect to the drug, combination of two different viscosity grades, % drug content in the formulation and the use of water soluble / insoluble fillers on the dissolution of metoprolol succinate was studied. The critical formulation parameters namely PEO concentration and % drug content were chosen as input factors and dissolution at 1, 4, 8 and 20 hours was recorded as responses to carry out optimization using the DOE approach. The results obtained after statistical treatment of data provided a design space that can be used for achieving the desired formulation profile. The model has been validated to predict the effect of the input factors (PEO type and concentration and % drug content) on the responses (in vitro dissolution).
 Keywords: Polyethylene Oxide, Modified Release Drug Delivery System, Metoprolol

Calcium Chloride Modified Alginate Microparticles Formulated by the Spray Drying Process: A Strategy to Prolong the Release of Freely Soluble Drugs.

Alginate (ALG) cross-linking by CaCl2 is a promising strategy to obtain modified-release drug delivery systems with mucoadhesive properties. However, current technologies to produce CaCl2 cross-linked alginate microparticles possess major disadvantages, such as a poor encapsulation efficiency of water-soluble drugs and a difficulty in controlling the process. Hence, this study presents a novel method that streamlines microparticle production by spray drying; a rapid, continuous, reproducible, and scalable technique enabling obtainment of a product with low moisture content, high drug loading, and a high production yield. To model a freely water-soluble drug, metformin hydrochloride (MF) was selected. It was observed that MF was successfully encapsulated in alginate microparticles cross-linked by CaCl2 using a one-step drying process. Modification of ALG provided drug release prolongation—particles obtained from 2% ALG cross-linked by 0.1% CaCl2 with a prolonged MF rate of dissolution of up to 12 h. Cross-linking of the ALG microparticles structure by CaCl2 decreased the swelling ratio and improved the mucoadhesive properties which were evaluated using porcine stomach mucosa.

Development of a Modified - release Drug Delivery System with Bexarotene Loaded in Clinoptilolite

Developing biomaterials with optimal loading properties and controlled release of drugs is a priority of medical research. Clinoptilolite is a natural zeolite used in various industrial processes. Its texture and structure recommend its use as a biocompatible matrix for the development of modified release drug delivery systems. The present study aims to develop and characterize modified-release systems based on bexarotene loaded clinoptilolite. Bexarotene is a retinoid that is used as an anticancer agent in the topical treatment of cutaneous T-cell lymphoma. By adding bexarotene to these systems, skin delivered antineoplastic therapy with bexarotene can be improved. Clinoptilolite was obtained by purifying the volcanic tuffs from Mirsid quarry, Salaj Romania. After thermal and chemical purification, two monoionic forms of clinoptilolite were obtained. They were labeled as Na-CLI and H-CLI, respectively. Their texture and structure were characterized by specific methods. Subsequently, these forms of clinoptilolite were used as hosts for bexarotene loading by wet impregnation. The obtained results showed that the two modified-release systems Bxt@Na and Bxt@H, respectively, have no incompatibilities and provide prolonged release of the drug.

FORMULATION AND EVALUATION OF ASPIRIN RELEASE FROM MATRIX PELLETS COMPRESSED INTO MUPS TABLET

MUPS (Multiple Unit Pellets System):
 The oral route of drug administration is the most important and most user-friendly route of administration. In recent years, Multiple Unit Pellet Systems (MUPS) tablets are widely used in solid dosage form design. MUPS is considered to provide pharmacokinetic advantages compared to monolithic dosage forms. Typically, modified release pellets are contained in MUPS tablets. Modified release drug delivery systems have acquired very important role in pharmaceutical research and development.1
 1.1Advantages of Compaction of MUPS over Conventional Modified-Release Tablets and/or Pellet-Filled Capsules and Tablets. 
 
 The compression of multiparticulates into tablets, unlike the hard gelatin capsule, is a tamper-proof dosage form and has greater physicochemical and microbiological stability of pellets as they are embedment in the inert matrix.
 Tablets have less difficulty in esophageal transport than capsules.
 Tablets containing coated subunits can be prepared at a lower cost than these subunits filled into hard gelatin capsules because of higher production rate of the tablet press.
 The expensive control of capsule integrity after filling is also eliminated.
 In addition, tablets containing multiparticulates without losing the controlled-release properties could be scored, which allow a more flexible dosage regimen.

Synthetic Zeolites as Controlled-Release Delivery Systems for Anti-Inflammatory Drugs.

Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment.

DESIGN, DEVELOPMENT AND IN VITRO EVALUATION OF MODIFIED RELEASE HYDROGEL BASED DRUG DELIVERY SYSTEMS OF OSELTAMIVIR PHOSPHATE

Hydrogels are 3-dimensional hydrophilic polymeric networks composed of homo or co-polymers capable of imbibing large amounts of biological fluids. They can be tailored as modified release dosage forms for both hydrophilic and hydrophobic drugs. The present study was aimed to develop and characterize oral hydrogel based drug delivery systems of Oseltamivir phosphate by physical cross-linking polymerization technique using guar gum and starch as hydrophilic carriers and hydroxy ethyl methacrylate. The hydrogel tablets were dried and the drug was loaded by imbibition from the drug solution. The compatibility of drug with the polymers was confirmed by Infrared spectroscopy. Differential scanning calorimetric studies confirmed the nature of the drug in the hydrogel formulations. Surface morphology studied by scanning electron microscopy revealed the rough and contour outer surface. The hydrogel tablets were further studied for entrapment efficiency, swelling kinetics at various pH and in vitro drug release. The results showed a good entrapment efficiency of about 85.6% and the swelling rate was found to be 98.33 at higher pH. The percentage drug release was also higher as the pH increased and was found to be highest in F4 formulation (87.39%) in 24 hrs. Further, the release kinetics was observed to follow first order, super case II transport mechanism. The stability studies showed that the hydrogel formulations prepared using starch, guar gum and hydroxy ethyl methacrylate offer good stability to the drug. It was hence concluded that the hydrogel drug delivery systems could be appropriate as a modified release drug delivery system.

Hydrophilic Polymers for Modified-Release Nanoparticles: A Review of Mathematical Modelling for Pharmacokinetic Analysis.

Hydrophilic polymers are the most common group of polymers used in the preparation of modifiedrelease drug delivery systems. This is due to their versatility, low cost, high production yield, as well as easy manufacturing and adequate in vitro/in vivo correlation. In normal physiological conditions, the matrix controls the release of the loaded drug over time through a process of diffusion and/or erosion of the matrix, depending on its physicochemical composition. This is particularly relevant when describing the pharmacokinetic profile of nanosized drug delivery systems (nanoparticles). The use of mathematical models became an important tool to characterize the pharmacokinetics of drugs loaded in nanoparticles to improve the drug bioavailability and to establish bioequivalence. Therefore, the drug release profile can be predicted by a minimum number of experimental studies, since the mathematical equations reveal the dissolution rate of the drug loaded in the hydrophilic matrix. The present paper discusses the use of mathematical models when developing modified-release drug delivery systems of nanometer size composed of hydrophilic polymers.

Comparative Study of Polycomplexes Based on Carbopol® and Oppositely Charged Polyelectrolytes as a New Oral Drug Delivery System

We report here a comparative study of the release of model drug diclofenac sodium from samples of interpolyelectrolyte complexes (IPEC) in in vitro conditions on a rotating basket apparatus and in vivo in experiments in rabbits. The study IPEC were prepared using different grades of Carbopol® polymer (C71g, C2020) and Noveon® AA-1 and oppositely charged polyelectrolytes – Eudragit® EPO or the natural polysaccharide low-viscosity chitosan. These studies demonstrated the potential for IPEC samples based on Carbopol® as a new modified-release drug delivery system. At the same time, assessment of bioadhesive properties provided evidence of the potential for using IPEC based on C2020/EPO as a mucoadhesive carrier.

Evaluation of in vivo behavior of controlled and pulsatile release pastilles using pharmacokinetic and γ-scintigraphic techniques

Objective: To evaluate the in vivo behavior of controlled and pulsatile release pastilles for chronic treatment of asthma and chronic obstructive pulmonary disease (COPD) and for the chronotherapeutic management of nocturnal asthma, respectively.Research design & methods: The prepared immediate release and controlled release pastilles were subjected to in vivo pharmacokinetic studies in rats. Whereas, pulsatile release formulation was subjected to γ-scintigraphic study in rats to study the gastrointestinal transit of the formulations and its results were correlated with the previous pharmacokinetic data.Results: The in vivo pharmacokinetic study of controlled release pastille formulation showed significant decrease in Cmax with increase in tmax, which indicates that the effect of dosage form would last for longer duration. Thus, the prepared formulation can be useful for the chronic treatment of asthma and COPD. The γ-scintigraphic study and pharmacokinetic data indicated that the pastilles coated with the enteric coat and the additional floating coat were effective in significantly delaying the in vivo drug release (by 4–5 h) required for the chronotherapeutic treatment of nocturnal asthma.Conclusion: This study opens a new alternative to the conventional tablet or capsule dosage form for the development of both immediate and modified release drug delivery systems.

Osmotically Controlled Drug Delivery System with Associated Drugs

Conventional drug delivery systems have slight control over their drug release and almost no control over the effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the controlled or modified release drug delivery systems. They include dosage forms for oral and transdermal administration as well as injectable and implantable systems. For most of drugs, oral route remains as the most acceptable route of administration. Certain molecules may have low oral bioavailability because of solubility or permeability limitations. Development of an extended release dosage form also requires reasonable absorption throughout the gastro-intestinal tract (GIT). Among the available techniques to improve the bioavailability of these drugs fabrication of osmotic drug delivery system is the most appropriate one. Osmotic drug delivery systems release the drug with the zero order kinetics which does not depend on the initial concentration and the physiological factors of GIT. This review brings out new technologies, fabrication and recent clinical research in osmotic drug delivery.

A More Relevant Dissolution Method for Evaluation of Floating Drug Delivery System

Introduction A modified release drug delivery system with prolonged residence time in the stomach is of particular interest for drugs: (a) that are locally acting in the stomach, (b) that have an absorption window in the stomach or in the upper part of small intestine, (c) that are unstable in the intestinal or colonic environments, or (d) have low solubility at high pH values. Systems that prolong the gastric residence time can also be used as sustained release devices with a reduced frequency of administration and therefore, can improve patient compliance (1). Approaches to increase gastric residence time include: (a) bioadhesive delivery systems that adhere to mucosal surfaces, (b) delivery systems that increase in size to retard passage through the pylorus, and (c) density-controlled delivery systems, that either float or sink in gastric fluids (2-6). In vitro dissolution testing is generally carried out for quality control purposes and to establish an in vivo in vitro correlation. Traditional in vitro dissolution methods have been shown to be poor predictors of in vivo performance for floating dosage forms (7).The currently used in vitro dissolution methods do not mimic the conditions present in the stomach. Researchers around the world have tried different methods for studying in vitro dissolution for floating drug delivery systems (8,9). However, each of the methods has some limitations. Hence, a modified in-vitro dissolution method was evaluated.

Physiologically based novel peroral modified release drug delivery system: Self-destructing hydrogel piston-pump

Peroral modified drug delivery systems on the market release fue drug by either 0-order, 1º-order, square root oftime or mixed rate. This means that the drugis released mto the gastrointestinallumenin amounts being either constantper unit of time or decreasingwith time. However, physiologically absorption from the GI lumen gets slower and more difficult past the small intestme. A novel drug delivery system is described far 24 horus drug delivery which follows approximate 0-orden release throughout the small intestine, but releases increasing amounts of drug once in the colon ta compensate for increasingly more difficult absorption. Nearly constant steady state drug plasma concentrations are achieved . The novel drug delivery system is a two layered dosage form with an immediate release layer and a modified release layer. The latter ene is a hydrogel piston pump comprised of a drug core layer and a hydrogel swelling layer, embedded into a semipermeable shell by compression coating. The upper site of the shell has a release channel in the center.

Polymers–gamma ray interaction. Effects of gamma irradiation on modified release drug delivery systems for oral administration

The aim of this work is to verify the efficiency of two kinds of matrix tablets formulations containing PEO or PVA as retarding polymer. Moreover, since in the last years the exposure to ionizing radiation is a more and more used method to reduce bacterial charge in pharmaceutical products, the effects of gamma irradiation on these two kinds of polymers has been evaluated. The study is performed on matrix tablets containing diltiazem HCl, as model drug, and polyethylene oxides (PEO) of two different molecular weights or polyvinylalchool (PVA) of medium degree of hydrolysis, as drug release modulators. Dissolution of the matrices, release of diltiazem and morphological behaviour of the samples, before and after exposure to increasing doses of gamma irradiation, are investigated in order to verify their stability. The results show that the ionizing radiation does not modify significantly the dissolution trend of the PVA samples; on the contrary, the dissolution and the morphological behaviour of the PEO matrices is strongly affected by the radiation dose received. In particular, the dissolution rate of the irradiated PEO tablets dramatically increases as a function of the irradiation dose and the swelling process, which characterised the non-irradiated PEO samples, was replaced by a rapid erosion process responsible for the quickly dissolution of the matrices. The changes of the dissolution and morphological PEO tablets performances could be explained by a breaking of the polymeric chains (shown by EPR studies) as a consequence of the exposure to gamma rays. These chemical–structural modifications of the polymers are responsible for the reduced efficacy of the PEO systems in controlling the drug release rate.

Chitinosans as tableting excipients for modified release delivery systems

The term ‘chitinosans’ embraces the spectrum of acetylated poly( N-glucosamines) ranging from chitin to chitosan. Chitinosans ( I), at acidic pH, have protonated amines which can interact with oppositely charged drug ions and, thereby, modify drug release from drug delivery systems. Tablets were compressed from a physical mixture containing salicylic acid ( II) as the model drug, I, and magnesium stearate. Five commercial I compounds, varying in degree of deacetylation and molecular weight, were selected. Tablets were compressed at 5000, 10 000, and 15 000 psig using a Carver and a single punch tablet press. The differential scanning calorimetry thermograms provided evidence of I– II interaction in the powder blend. Analysis of variance (ANOVA) indicated that the compression pressure did not significantly affect the crushing strength (CS) or the release profile of II from the I-matrix tablets ( P>0.05). Furthermore, the ANOVA also indicated that the tablet press used during manufacture did not affect the above properties ( P>0.05); however, the chitinosans significantly affected the CS as well as the release profile of II from I-matrix tablets ( P<0.05). This study provides further evidence for the use of commercial I compounds as excipients for use in modified release drug delivery systems.