Release Drug Delivery System Research Articles

Preparation and Evaluation of a Novel Oral Microemulsion Drug Delivery System for Enhancing the Bioavailability of Diltiazem

Diltiazem, a calcium ion cellular influx inhibitor is known for its limited and variable bioavailability. This study is intended to explore the benefits of microemulsion formulation as an oral drug delivery system for immediate release to improve the bioavailability and efficacy of Diltiazem. Methods: Oil in water microemulsion was prepared using the simple water titration method. The optimized formulation was evaluated for physicochemical parameters like viscosity, pH, conductivity, and accelerated stability studies. In vitro release, diltiazem microemulsion was investigated.

Targeted Delivery of Narrow-Spectrum Protein Antibiotics to the Lower Gastrointestinal Tract in a Murine Model of Escherichia coli Colonization.

Bacteriocins are narrow-spectrum protein antibiotics that could potentially be used to engineer the human gut microbiota. However, technologies for targeted delivery of proteins to the lower gastrointestinal (GI) tract in preclinical animal models are currently lacking. In this work, we have developed methods for the microencapsulation of Escherichia coli targeting bacteriocins, colicin E9 and Ia, in a pH responsive formulation to allow their targeted delivery and controlled release in an in vivo murine model of E. coli colonization. Membrane emulsification was used to produce a water-in-oil emulsion with the water-soluble polymer subsequently cross-linked to produce hydrogel microcapsules. The microcapsule fabrication process allowed control of the size of the drug delivery system and a near 100% yield of the encapsulated therapeutic cargo. pH-triggered release of the encapsulated colicins was achieved using a widely available pH-responsive anionic copolymer in combination with alginate biopolymers. In vivo experiments using a murine E. coli intestinal colonization model demonstrated that oral delivery of the encapsulated colicins resulted in a significant decrease in intestinal colonization and reduction in E. coli shedding in the feces of the animals. Employing controlled release drug delivery systems such as that described here is essential to enable delivery of new protein therapeutics or other biological interventions for testing within small animal models of infection. Such approaches may have considerable value for the future development of strategies to engineer the human gut microbiota, which is central to health and disease.

Formulation and Development Matrix Tablets Of Methimazole

Methimazole is active pharmaceutical ingredient effectively utilized in hyperthyroidism. Methimazole inhibits peroxidase as well as iodine interactions with thyroglobulin to produce triiodothyronine with thyroxine. Methimazole shows very low protein binding (1-10%) bounds to plasma proteins and easily metabolized by liver. In this investigation, efforts given to develop a sustained release matrix tablet of Methimazole. Sustained release drug delivery systems are for a maximum of 24 hours clinical effectiveness. Such systems are primarily for the drugs of short elimination half-life. However, drugs with long half-life also qualify if a reduction in steady state fluctuation is desired. Matrix tablets of methimazole were prepared by utilizing direct compression method. HPMC along with Sodium carboxy methyl cellulose used to retard drug release from the dosage form. Matrix tablets of methimazole were evaluated for different quality control test to improve quality of the product. In vitro release study of methimazole matrix tablets shows that polymer percentage used in the formula is enough to extend the release of the drug for at least 12 hr. In dissolution study of matrix of methimazole formulation F2 shows maximum drug release 97.93 % at the end of 6 hours while F1 shows least 83.64 %. Keywords: Matrix tablet, Methimazole, Sustained Release

Evaluation of Inflammatory Response Due to Use of Controlled Release Drug Delivery System of Chitosan Hydrogel Loaded with Buprenorphine and Ketorolac in Rat with Experimental Proximal Tibial Epiphysis Defect

Aims: A controlled release drug delivery system loaded with buprenorphine and ketorolac was synthesized and used in the experimental model of bone defect and while evaluating the inflammatory response, the repair process in the defects was investigated. Materials and methods: To determine the effectiveness of the synthesized the mentioned systems, 5 groups were defined; the control group, the chitosan hydrogel receiving group (chitosan group), the ketorolac-loaded chitosan hydrogel group (ketorolac group), the buprenorphine-loaded chitosan hydrogel receiving group (buprenorphine group), and the chitosan hydrogel-loading group loaded with a combination of ketorolac and buprenorphine (ketorolac-buprenorphine group). Results: The results showed that the population of leukocytes (tWBC) and neutrophils on different days of the study in the control group compared to other groups had a significant increase (P < 0.05) while on day 7 of the study in the ketorolac group these parameters decreased significantly compared to other groups (P < 0.05). While examining the histological changes in the experimental defect created in the proximal tibia of rats at different times, some inflammatory indices such as total and differential leukocyte population, plasma concentrations of TNF-α and IL-6 were compared in different groups (P < 0.05). The various evaluated data showed that among the different groups, in the control and ketorolac-buprenorphine groups, there was the lowest and highest control of inflammatory response and bone repair, respectively. Conclusion: In the ketorolac group due to the impact of ketorolac on leukocyte populations the best bone healing can be expected among the different treatment groups.

Ambient pressure drug loading on trimethylchlorosilane silylated silica aerogel in aspirin controlled-release system

Trimethylchlorosilane silylated silica aerogel (TS-SA) was loaded with a model drug, aspirin. TS-SA preparation, drug loading, and drying were performed through ambient pressure techniques in a safe and cheap manner. The sample structure, drug loading, and drug dissolution profiles were characterized by N2 adsorption and desorption analysis, FT-IR spectroscopy, UV absorption spectroscopy, FE-EM, EDX, XRD, and DSC. The characterization results indicated drug molecules are successfully loaded on the entire nanostructure of TS-SA. Specific surface area, total pore volume, and average pore size decrease with drug loading in TS-SA structure, as well as XRD and DSC results are indicating the amorphous state of loaded aspirin. Drug adsorption isotherm was measured and fitted well by the Freundlich model. Drug release kinetics from the samples were also evaluated in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 7.4). The zero-order model, the first-order model, and the Higuchi model were employed to study the release kinetics. Better fitting to the Higuchi model showed that Fick's diffusion governs the aspirin release mechanism. The release rate of loaded samples was slower than the pure drug in both HCl and phosphate buffer. As pure aspirin dissolves totally in 0.1 N HCl and phosphate buffer within 40 min and 20 min, respectively, loaded drug dissolve 35% ± 4 and 80% ± 4 in 0.1 N HCl and phosphate buffer within 100 min. The ambient pressure drug loading on TS-SA could have interesting potential applications in controlled release drug delivery systems.

Design and evaluation of chitosan-amino acid thermosensitive hydrogel.

Chitosan/glycerophosphate thermosensitive hydrogel crosslinked physically was a potential drug delivery carrier; however, long gelation time limits its application. Here, chitosan-amino acid (AA) thermosensitive hydrogels were prepared from chitosan (CS), αβ-glycerophosphate (GP), and l-lysine (Lys) or l-glutamic acid (Glu). The prepared CS-Lys/GP and CS-Glu/GP hydrogel showed good thermosensitivity and could form gels in a short time. The optimal parameters of CS-Lys/GP hydrogel were that the concentration of CS-Lys was 2.5%, the ratio of CS/Lys was 3.5/1.0, the ratio of CS-Lys/GP was 4.5/1.0. The optimal parameters of CS-Glu/GP hydrogel were that the concentration of CS-Glu was 3.0%, the ratio of CS/Glu was 2.0/1.0, and the ratio of CS-Glu/GP was 4.0/1.5. Chitosan-amino acid (CS-AA) thermosensitive hydrogel had a three-dimensional network structure. The addition of model drug tinidazole (TNZ) had no obvious effect on the structure of hydrogel. The results of infrared spectroscopy showed that there were hydrogen bonds between amino acids and chitosan. In vitro release results showed that CS-Lys/GP and CS-Glu/GP thermosensitive hydrogels had sustained release effects. Thus, the chitosan-amino acid thermosensitive hydrogels hold great potential as a sustained release drug delivery system.

FORMULATION AND EVALUATION OF METFORMIN HYDROCHLORIDE SUSTAINED RELEASE MATRIX TABLETS

Objective: Now a days as very few antidiabetic drugs are coming out of research and development and some existing drugs are showing several side effects when administered orally, multiple times in a day, hence change in the operation is a suitable and optimized way to make some drug more effective by slight alteration in the drug delivery. Matrix type drug delivery systems of an antidiabetic drug like Metformin Hydrochloride, is an interesting and promising option when developing an oral sustained release system&#x0D; Methods: An appropriately designed controlled release drug delivery system can be a major advance towards solving problems concerning the targeting of a drug to a specific organ or tissue and controlling the rate of drug delivery to the target sites. This research work is made in designing of sustained release dosage form of Metformin Hydrochloride by wet granulation method employing both Xanthan Gum and Hydroxy Propyl Methyl Cellulose (HPMC K4M) as a rate controlling polymer.&#x0D; Results: The development of oral sustained release systems has been a challenge to formulation scientists due to their inability to restrain and localize the system at targeted areas of the gastrointestinal tract. From all the formulation trial batches, formulation F7 shows the best results. It has been observed that HPMC K4M alone cannot give satisfactory drug release profile but the blend of HPMC K4M and Xanthan gum together give the best drug release kinetics.&#x0D; Conclusion: The drug release mechanism from the matrix tablets follows Fickian diffusion with first order kinetics. Thus, sustained release matrix tablets of metformin hydrochloride can be expected to reduce the frequency of administration and decrease the dose dependent side effects

Implementation of Quality by Design Principles for the Evolution of Optimized Sustained Release Drug Delivery System

Aim: The aim of the present work is the implementation of Quality by Design principles for the evolution of optimized sustained release drug delivery system. Background: Quality by Design (QbD) approach refers to an advance approach to develop an optimized dosage form. QbD has become a vital modern scientific approach to develop a quality dosage form. In the modern era of science, researchers can develop an optimized dosage form with least effort, money and manpower. Objectives: Objective of the research work was the successful development of optimized floating bioadhesive tablets of glipizide using floating-bioadhesive potential of cellulosic polymer and carbomersusing quality by design (QbD) approach. Methods: Quality Target Product Profile (QTPP) of drug delivery system was defined as well as critical quality attributes (CQAs) were identified. A face centered central composite design (CCD) was utilized in assessing the impact of the individual critical material attribute (CMA) like Hydro Propyl Methyl Cellulose K4M(HPMC K4M)and Carbopol 934P (CP 934P) and their interactions, using least experimentation. Formulations were developed and quantitative impact on CQAs was determined using mathematical model. The optimized formulation was obtained and characterized for in-vitro as well as in-vivo parameters. Results: A Fishikawa diagram and Failure Mode and Effect Analysis (FMEA) was performed to identify potential failure modes associated with the dosage form. The optimum formulation was embarked upon using mathematical model developed yielding desired CQAs followed for confirmation of data. Sustained release drug delivery system was successfully developed by using QbD approach. In-vivo X-ray imaging in rabbit and γ-scintigraphic study in manconfirmed the buoyant nature of the mucoadhesive floating tablet for 8 h in the upper gastrointestinal tract. Conclusion: Optimized formulation shows phenomenal floating, bioadhesive properties and drug release retardation characteristics, utilizing a mixture of cost-effective polymers Hence, QbD approach may be regarded as an important tool in development of floating bioadhesive CR dosage forms.

Raft Forming Systems: A Novel Approach to Gastric Retention

&#x0D; Oral delivery of drug is the most preferable drug delivery due to the ease of administration, patient compliance and flexibility in the formulations. In recent era various technologies have been made in research and development of oral controlled release drug delivery system to overcome various physiological difficulties such as variation in gastric retention and emptying time. Conventional oral dosage forms pose low bioavailability problems due to their rapid gastric transition from stomach, especially in case of drugs which are less soluble at alkaline pH of intestine and locally acting drugs in stomach get rapidly emptied. So, frequency of dose administration in such cases is increased. Gastro retentive drug delivery system (GRDDS) is facing many challenges which can be overcome by upcoming newly emerging approach, raft forming systems (RFS). The present study provides valuable information and highlights advances in this raft forming system. Different types of smart polymers used for their formulation have also been summarized. The current review focuses on the mechanism, formulation development and evaluation aspects of the raft forming systems and also highlights parameters which may lead to response variations in altered physiological conditions are discussed as well.

FORMULATION DEVELOPMENT AND EVALUATION OF MATRIX TABLET TRAZODONE HYDROCHLORIDE USING NATURAL POLYMER

Increased complications and costs of marketing of innovative drugs focused greater attention to the development of sustained release (SR) or controlled release (CR) drug delivery systems. Trazodone Hydrochloride (TRZ) is a well-known chemical compound that is used as an antidepressant that belongs to a selective serotonin reuptake inhibitor (SARI). The objective of present work was to develop and evaluated oral sustained release matrix tablet of TRZ. Pre-compression parameters were evaluated. The tablets were evaluated for post-compression parameters such as thickness, hardness, average weight, friability and In vitro release studies. No interactions were observed between TRZ and excipients from the Fourier transform infrared spectroscopy. The present research work was successful in improving the efficacy TRZ oral therapy as the drug release was extended for 12 hours thus reducing dosing frequency thereby improving patient compliance. The study also revealed the applicability of HPMC K-15, Gaur gum and PVP K30 as rate-controlling polymers in matrix tablets. The hydrophilic matrix of HPMC alone cannot control the release TRZ effective for 12 h while when combined with guar gum, may slow down the release of the drug and therefore, can be successfully employed for the formulation of matrix tablets SR. It may be concluded from the study that; the optimized formulation F-8 was shown maximum drug release 99.12 % in 12 h of dissolution. The release kinetic data of formulation F-8 shown first order release kinetics (R2 = 0.980).

PH-responsive and sustained release drug delivery system of BSA coated CDs-DOX

BackgroundThe drugs are easily cleared and lack of targeting in chemotherapy, thus reducing its efficacy. A novel pH- responsive drug delivery system based on carbon quantum dots (CDs) was proposed. CDs have low toxicity and good biocompatibility and can be electrically combined with doxorubicin (DOX). The bovine serum albumin (BSA), an endogenousx substance, could be used as a protein model for constructing a novel lipoprotein-like nanocarrier. In this study, we introduced BSA into the drug delivery system and prepared a stable drug delivery system BSA@CDs-DOX. The system was characterized by UV-Vis, fourier infrared spectroscopy, transmission electron microscopy and fluorescence spectroscopy, and its stability, drug loading efficiency, coating efficiency and drug release in vitro were investigated. The release of drug from the system was tracked by the fluorescence properties of CDs. ResultsThe stability of the BSA@CDs-DOX system was obviously enhanced in various environments. The in vitro release profile was prolonged, and the cumulative release ratio at pH = 5.0 was 7.5 times higher than that at pH = 7.4. The drug side effects on the normal cells were significantly reduced and the killing effect on cancerous cells was improved in longer time. Excellent and sustained migration resistance was observed in 72 h. The drug uptake process and cellular state were evaluated visually in real time until 72 h. ConclusionThe stable and sustained release BSA@CDs-DOX system showed good application prospect in chemotherapy of tumors.

An Update on the Recent Advances in Cubosome: A Novel Drug Delivery System.

Cubosomes are highly stable nanostructured liquid crystalline dosage delivery form, derived from amphiphilic lipids and polymer-based stabilizers converting it in a form of effective biocompatible carrier for the drug delivery. The delivery form comprised of bicontinuous lipid bilayers arranged in three-dimensional honeycombs like structure provided with two internal aqueous channels for the incorporation of many s biologically active ingredients. In contrast to liposomes, they provide a large surface area for the incorporation of different types of ingredients. Due to the distinct advantages of biocompatibility and thermodynamic stability, cubosomes have remained the first preference as a method of choice in the sustained release, controlled release, and targeted release dosage forms as new drug delivery system for the better release of the drugs. As a lot of advancement in the new form of dosage form brought the novel avenues in drug delivery mechanisms, so it was a matter of worth to compile the latest updates on the various aspects of the mentioned therapeutic delivery system including its structure, routes of applications along with the potential applications to encapsulate variety drugs to serve health-related benefits.

Technologies in Bilayer Tablet Manufacturing: A Review

Bilayer tablet is a recent time for the successful development of controlled release formulation along with various quality to provide a way of the successful drug delivery system. Over the past 30 years stated that the cost and complications involved in marketing new drug entities have increased, with consequent recognition of therapeutic advantages of controlled drug delivery, greater attention has been concentration on development of sustained or controlled release drug delivery systems. Bilayer tablet it is used in the different aspect for anti-inflammatory and analgesic. Bilayer tablet incidental release of two drugs in combination, separate two incompatible substance and also for sustained release tablet in which one layer is immediate release as initial dose and second layer is maintenance dose. Bilayer tablet is enhancing beneficial technology to control the shortcoming of the single layered tablet. There is various application used in the bilayer tablets.

Development and quality evaluation of chitosan-coated cellulose acetate phthalate-poloxamer enamel adhesive device for the treatment of dentin carious lesion

The present study was aimed to develop chitosan-coated enamel adhesive device of CAP-P 407 (Cellulose acetate phthalate-Poloxamer 407), loaded with MNC (Minocycline) for sustained release and site-specific drug delivery system for the carious lesion. The average tensile strength and in-vitro drug release of uncoated dental film were found to be 15.97 kg/mm2 and 98.11% in 24 h, respectively. The average in-vitro mucoadhesion time and tooth adhesion strength of the finished product was found to be 249 minutes and 268 g, respectively. In-vitro antimicrobial study showed the drug concentration is well above MIC even after 8 hours of drug release.

A Review on Tablet Dosage Form: Recent Advancements with Special Emphasis on Rapid Disintegrating Tablet

Tablets are the most commonly prescribed dosage form as offer a convenient form of drug administration provides dosage uniformity from tablet to tablet, stable over extended and diverse storage conditions, can be produced on high-speed compression, labelling, and packaging equipment. Advancements in technology and modification in standard compressed tablet are to achieve better acceptability as well as bioavailability. Various types of newer and more efficient tablets are developed to create a delivery system that is relatively simple to administration. In one sense osmotic pump systems are another type of membrane-controlled release drug delivery system and work in the following way. Drug is incorporated in a tablet core which is water soluble, and which will solubilize or suspend the drug in the presence of water. Also, a multi-layer tablet dosage form over a more conventional mono-layer tablet is useful. In FDDS Gastro retentive dosage form improves bioavailability, therapeutic efficacy and allows a reduction in the dose because of steady therapeutic levels of drug. The another system is MADDS Mucoadhesion is commonly used to describe an interaction between the mucin layer, which lines the entire GI tract, and a bio adhesive polymer, which could be natural or synthetic in origin. An ideal controlled drug delivery system is one which delivers the drugs at a predetermined rate, locally or systematically, for a specified period of time and an ideal targeted drug delivery system is the one which delivers the drugs only to its sites of action and not to the non-targeted organs or tissues. So, in this review article we will study the basic fundamentals of tablets their technologies, and types of systems with available marketed products of various dosage forms.

Preparation of Magnetic-Luminescent Bifunctional Rapeseed Pod-Like Drug Delivery System for Sequential Release of Dual Drugs.

Drug delivery systems (DDSs) limited to a single function or single-drug loading are struggling to meet the requirements of clinical medical applications. It is of great significance to fabricate DDSs with multiple functions such as magnetic targeting or fluorescent labeling, as well as with multiple-drug loading for enhancing drug efficacy and accelerating actions. In this study, inspired by the dual-chamber structure of rapeseed pods, biomimetic magnetic–luminescent bifunctional drug delivery carriers (DDCs) of 1.9 ± 0.3 μm diameter and 19.6 ± 4.4 μm length for dual drug release were fabricated via double-needle electrospraying. Morphological images showed that the rapeseed pod-like DDCs had a rod-like morphology and Janus dual-chamber structure. Magnetic nanoparticles and luminescent materials were elaborately designed to be dispersed in two different chambers to endow the DDCs with excellent magnetic and luminescent properties. Synchronously, the Janus structure of DDCs promoted the luminescent intensity by at least threefold compared to single-chamber DDCs. The results of the hemolysis experiment and cytotoxicity assay suggested the great blood and cell compatibilities of DDCs. Further inspired by the core–shell structure of rapeseeds containing oil wrapped in rapeseed pods, DDCs were fabricated to carry benzimidazole molecules and doxorubicin@chitosan nanoparticles in different chambers, realizing the sequential release of benzimidazole within 12 h and of doxorubicin from day 3 to day 18. These rapeseed pod-like DDSs with excellent magnetic and luminescent properties and sequential release of dual drugs have potential for biomedical applications such as targeted drug delivery, bioimaging, and sustained treatment of diseases.

Polyelectrolyte complexes of chitosan and sodium alginate as a drug delivery system for diclofenac sodium

AbstractPolyelectrolyte complexes (PECs) have unique physicochemical properties which make them very interesting for pharmaceutical applications and particularly as drug delivery systems. The aim of this work was to obtain PECs based on the biocompatible and biodegradable biopolymers chitosan and sodium alginate and to apply them as a drug delivery system for sustained release of diclofenac sodium. Three complexes with different ratios between the two polyions were obtained. Their structure and properties were investigated using dynamic light scattering, microscopy methods (optical, scanning and transmission electron microscopy), infrared spectroscopy, X‐ray diffraction. The drug entrapment efficiency of the various PECs was assessed and the release profiles were monitored. In this way the relationship between the composition of the PECs and the drug release profiles was outlined. The fibrillar form of the chitosan/alginate PECs was demonstrated to exert specific control over the diclofenac release which makes these materials appropriate as vehicles for controlled diclofenac sodium release. © 2021 Society of Industrial Chemistry.

Synthesis and testing of polymer grafted mesoporous silica as glucose-responsive insulin release drug delivery systems

Stimuli-responsive materials based on mesoporous silica have been widely studied for the controlled release of drugs. Glucose-responsive systems play a vital role in the controlled release of insulin because they can smartly adjust the amount of released insulin in response to the fluctuational blood glucose concentration. Here, the mesoporous silica (MS) was modified with 3-fluoro-4-carboxyphenylboronic acid (FCPBA) to prepare phenylboronic acid-modified mesoporous silica (MS-FCPBA). N-acryloyl glucosamine (AGA) was copolymerized with N-isopropyl acrylamide (NIPAM) and acrylic acid (AAc) respectively to synthesize two polymers with diol groups, noted as P(NIPAM-co-AGA) and P(AAc-co-AGA) respectively. Since the phenylboronic acid group can form a borate ester bond with the diol group, the polymers were coated on the surface of insulin-loaded MS-FCPBA to obtain the insulin release systems. The results showed that the loading capacity and encapsulation efficiency of insulin could reach 14.7% and 85.9%, respectively. The two systems exhibited different glucose-responsive performance.

Albendazole Release from Silica-Chitosan Nanospheres. In Vitro Study on Cervix Cancer Cell Lines.

In this work, a pH-responsive drug-carrier based on chitosan-silica nanospheres was developed as a carrier for Albendazole (ABZ), a poorly water-soluble anthelmintic drug. Spherical silica nanoparticles were obtained by Stöber method and further etched to obtain mesoporous particles with sizes ranging from 350 to 400 nm. The specific BET area of nanoparticles increased from 15 m2/g to 150 m2/g for etched silica, which also exhibited a uniform pore size distribution. X-ray powder diffraction showed the presence of amorphous phase of silica and a low-intensity peak attributed to ABZ for the drug-loaded nanoparticles. A uniform layer of chitosan was obtained ranging from 10 to 15 nm in thickness due to the small concentration of chitosan used (0.45 mg of chitosan/mg of SiO2). The in vitro evaluation of hybrid nanoparticles was performed using four cervical cancer cell lines CaSki, HeLa, SiHa and C33A, showing a significant reduction in cell proliferation (>85%) after 72 h. Therefore, we confirmed the encapsulation and bioavailability of the drug, which was released in a controlled way, and the presence of chitosan delayed the release, which could be of interest for the development of prolonged release drug delivery systems.

Formulation and Invitro Characterization of Fluvoxamine Loaded Nanoparticles

Fluvoxamine is an antidepressant that functions pharmacologically as a selective serotonin reuptake inhibitor. Though it is in the same class as other SSRI drugs, it is most often used to treat obsessive-compulsive disorder. As the biological half-life of the drug is 15.6 hrs and belongs to BCS class II. To overcome these problems, Nanoparticles of Fluvoxamine were formulated by using Ethyl Cellulose, Eudragit RS 100 &amp; Eudragit Rl 100 as a polymer by emulsification method. Among all the 9 formulations F6 formulation is optimized, as it shows maximum drug release at the end of 12hrs which suits the controlled release drug delivery system criteria as per our studies, having acceptable particle size, SEM, and Zeta potential value. From the drug release kinetics of the F8 formulation of Losartan Nanoparticles dispersion, it was concluded that the F8 formulation follows Zero-order drug release with super case II transport mechanism.