Sustained Release Dosage Research Articles

Formulation and Evaluation of Glipizide-loaded Mucoadhesive Microparticle Using Salvia hispanica Seeds Mucilage as Co-polymer

Aims: Chia seed (Salvia hispanica L.) gum is a mucoadhesive, biodegradable polymer with sustained release properties. Objective: The objective of this study was to compare different formulations of glipizide-loaded microparticles using chia seed mucilage and sodium alginate, focusing on sustained release and mucoadhesive properties. Background: The present study aimed to comparatively evaluate various eco-friendly formulations of glipizide-loaded microparticles prepared using chia seed mucilage and sodium alginate. Materials and Methods: Gum was extracted from chia seeds and lyophilized, and preformulation studies were performed according to established protocols. Microparticles were formulated using the ionic gelation method, with sodium alginate as a copolymer and zinc chloride as a cross-linking agent. The prepared microparticles were evaluated using scanning electron microscopy (SEM) for size and particle aggregation, and Fourier Transform infrared spectroscopy (FTIR) for drug-polymer interaction, entrapment efficiency, swelling index, and in vitro drug release. Results: The % yield of chia seed mucilage was 27.35%. The pH of the mucilaginous suspension was 4.67 ± 0.50. The moisture content value was 14.56 % ± 0.50. The values of Carr's index and Hausner's ratio were 22.58 ± 1.89 and 1.38 ± 0.05, respectively. FTIR spectra showed no interaction between pure glipizide and chia seed mucilage, confirming no possible change in glipizide's pharmacology. SEM studies have confirmed the shape of the microparticles to be spherical, with average sizes ranging from 1235.18 ± 8.7 to 1423.25 ± 9.5 µm, and the drug entrapment efficiency ranged from 64.25 ± 2.52 to 81.82 ± 7.56%. The release of glipizide from the microparticles was sustained, and the Higuchi and Korsmeyer-Peppas models were found to be the best-fit kinetic models. Conclusion: The promising copolymer blend of chia seed mucilage and sodium alginate was used for the development of sustained-release dosage forms. A copolymer blend with a ratio of 1:1 produced glipizide-loaded microparticles with sustained release profiles and good mucoadhesive ability, along with a high percentage of drug entrapment efficiency.

Formulation and Evaluation of Sustained Release Dosage Form of Venlafaxine Hydrochloride for Enhanced Treatment of Neurodisorders

In the present study, we have designed and developed a sustained-release tablet formulation of Venlafaxine Hydrochloride. The optimized formulation was then subjected to various evaluation parameters. The formulation of venlafaxine hydrochloride sustained release tablets with a dosage of 500 mg included the utilization of several hydrophilic polymers, including jackfruit mucilage, HPMC K4, and PVPK30, as release retardants. This was done to extend the duration of drug release to 12 hours. The formulation features, including pre-compression and post-compression investigations, were conducted individually according to established protocols. The tablets were determined to be compliant in terms of weight uniformity, hardness, thickness, diameter, friability, and drug content. Separate in-vitro dissolution studies were done for both tablets. The venlafaxine hydrochloride SR formulation F18 was optimized to provide the desired release profile for up to 12 hours. The Venlafaxine Hydrochloride SR formulation was optimized and exhibited zero-order release kinetics. The stability studies conducted under accelerated conditions at a temperature of 40 ± 2°C and a relative humidity of 75 ± 5% yielded good results. The study indicated that the sustained release administration of Venlafaxine HCl is potentially efficacious. It reduces the frequency at which the patient has to take medication and improves patient adherence. Our objective is to conduct in-vivo pharmacokinetic studies of the formulation to verify the drug’s entry into the systemic circulation.

Multifunctional injectable microspheres for osteoarthritis therapy via spatiotemporally modulating macrophage polarization and inflammation

Local injection of anti-inflammatory drugs for osteoarthritis emerged as a promising administration in the clinic, and sustained-release dosage forms have great potential for future therapeutic applications. Controlling the response of patients only in the acute inflammatory phase is currently the focus of therapeutic interventions. To relieve acute pain in patients and to improve the long-term prognosis effect of osteoarthritis treatment, we designed a two-pronged approach in this research: an injectable double-layer microsphere containing a “nonsteroidal anti-inflammatory drug - macrophage polarizing factor” was constructed. The results indicated that microspheres could regulate the intra-articular environment by inhibiting local inflammatory cytokine production, promoting macrophage polarization to the M2-phenotype, and increasing the expression of cartilage repair factors. Polymers chosen could govern the biocompatibility of microspheres and control the release sequence of the two drugs. Injection of microspheres into the degenerative articular cavity of rats leads to suppressed inflammation and well-promoted cartilage regeneration.

Design, development, and optimization of sumatriptan loaded ethosomal intra-nasal nanogel for brain targeting

Background: Sumatriptan is one of the most essential drugs for treating migraine. However, dosage-related side effects are still a worry despite its 14 % oral bioavailability and recurrence of migraine-associated diseases. Methodology: The fundamental focus of the study is to develop the sumatriptan intra-nasal nano-ethsomal gel by film hydration technique with the aid of QbD principles that govern the varied compositions and blends of polymers like HPMC K100M and Phospolipon 90G to develop a sustained release dosage form. Results and discussion: The preliminary FT-IR and DSC studies revealed no interactions between the drug and their physical mixtures. The present study considered three observable responses: vesicle size, zeta potential, and percent drug release after 24 h, taken into consideration during the optimization of the ethosomal formulations utilizing 32 central composite designs (CCD). The vesicle size (122.23 nm), zeta potential (-40.2 mV), and drug release percentage (92.61 %) for all formulations were seen in the F12 batch after 24h. The p-XRD and SEM studies indicated that the nano-ethosomal gel was stable. The stability studies indicated the preparation of a more stable formulation for the parameters under the study protocol. Conclusion: Using a novel intra-nasal brain targeting approach by adapting the film hydration technique, the current issues might be addressed, and the drug's duration of residence at the absorption site uptake substantially increase. To efficiently modify the drug's residence through the intra-nasal route, this work focuses on developing a nano-ethosomal gel loaded with sumatriptan.

Sustained release delivery of favipiravir through statistically optimized, chemically cross-linked, pH-sensitive, swellable hydrogel

In the current work, favipiravir (an antiviral drug) loaded pH-responsive polymeric hydrogels were developed by the free redical polymerization technique. Box-Behnken design method via Design Expert version 11 was employed to furnish the composition of all hydrogel formulations. Here, polyethylene glycol (PEG) has been utilized as a polymer, acrylic acid (AA) as a monomer, and potassium persulfate (KPS) and methylene-bisacrylamide (MBA) as initiator and cross-linker, respectively. All networks were evaluated for in-vitro drug release (%), sol-gel fraction (%), swelling studies (%), porosity (%), percentage entrapment efficiency, and chemical compatibilities. According to findings, the swelling was pH sensitive and was shown to be greatest at a pH of 6.8 (2500%). The optimum gel fraction offered was 97.8%. A sufficient porosity allows the hydrogel to load a substantial amount of favipiravir despite its hydrophobic behavior. Hydrogels exhibited maximum entrapment efficiency of favipiravir upto 98%. The in-vitro release studies of drug-formulated hydrogel revealed that the drug release from hydrogel was between 85 to 110% within 24 h. Drug-release kinetic results showed that the Korsmeyer Peppas model was followed by most of the developed formulations based on the R2 value. In conclusion, the hydrogel-based technology proved to be an excellent option for creating the sustained-release dosage form of the antiviral drug favipiravir.

Compritol®-based solid lipid nanoparticles of desvenlafaxine prepared by ultrasonication-assisted hot-melt encapsulation to modify its release.

Aims: Desvenlafaxine (DES) in conventional dosage forms shows initial burst release after oral administration, leading to exaggeration of its side effects. These side effects can be overcome by a sustained-release dosage form using the chemically inert, low-melting-point lipid Compritol® 888 ATO, as it reduces initial burst release. Materials & methods: The potential of DES-loaded solid lipid nanoparticles (DES-SLNs) synthesized by ultrasonication-assisted hot-melt encapsulation to modify the release of DES was investigated. Results: The entrapment efficiency of DES-SLNs was 65.90% with the in vitro release profile showing a sustained-release behavior achieving 81% cumulative release within 16h without initial burst release. Conclusion: DES-SLNs are a potential carrier for sustained release of water-soluble antidepressant drugs such as DES.

Vildagliptin Sustained-release and Dapagliflozin Fixed-dose Combination in the Management of Type 2 Diabetes Mellitus: A Comprehensive Review

Type 2 diabetes mellitus (T2DM) is a complex disease with multiple pathophysiological defects and generally requires a combination of antidiabetic agents to achieve glycemic targets. In this context, a fixed-dose combination (FDC) of dipeptidyl peptidase-4 inhibitors vildagliptin sustained-release (SR) and a sodium-glucose cotransporter type 2 inhibitors dapagliflozin appear to be an attractive approach. There is a strong rationale for combining vildagliptin with dapagliflozin. They have complementary mechanisms of action that address several pathological pathways and are effective at all disease stages. Vildagliptin and dapagliflozin are generally well tolerated, with low hypoglycemia risk. Moreover, they exert beneficial pleiotropic actions on the cardiovascular system and kidneys, lower body weight, and blood pressure and reduce pill burden, providing an important option for managing a broad patient population. For Indian T2DM patients, who have a high prevalence of cardiometabolic risk factors, this combination would be an appropriate choice. Furthermore, the once-daily 100 mg SR dosage of vildagliptin meets the requirements for compliance and adherence. However, data on the vildagliptin SR and dapagliflozin FDC are limited. This review summarizes the available evidence and provides rational, practical guidance for the optimal clinical use of vildagliptin SR and dapagliflozin FDCs in T2DM patients.

An easy approach towards once a day sustained release dosage form using microporous Cu-MOFs as drug delivery vehicles

Metal–organic frameworks (MOFs) have potential as drug carriers on the basis of their surface areas and pore volumes that allow for high drug loading and fast release.

Feasibility study of sustained release dosage forms for incrementally modified drug by domestics pharmaceutical industry in Thailand

Background Incrementally modified drugs (IMDs) are anticipated to improve drug efficacy and compliance. Compared to new chemical entities, the research and development costs for IMDs are lower. The domestics industry currently focuses on manufacturing both generic and new generic drugs. To promote the growth of the industry, it is crucial to investigate the feasibility of developing IMDs. Methods This necessitates evaluating all five aspects, including needs, market, scientific, technological, and regulatory feasibility from January to December 2022. A mixed methods approach, combining literature review and in-depth interviews conducted online via Zoom. Qualitative data analysis will be performed through thematic analysis. Results Needs: medical needs, six out of seven physicians expressed a preference for sustained release (SR). The domestics industry is actively engaged in the research and development of SR as well. Market feasibility: The compound annual growth rate for SR in 2019 was found to be 3.97 percent, SR encompassing all nine of the 14-drug group. Scientific feasibility is not a concern as the industry has the capability to develop drugs. Technological feasibility: The IMDs technology readiness level is at level 4 (high level). The manufacturing of SR utilizes a matrix technique, membrane system, and pellets. Regulatory feasibility: Although have registration guidelines for IMDs, no industry has successfully registered IMDs yet. Conclusions SR has demonstrated feasibility for IMDs development in all aspects except for the challenging issue of drug registration.

Improved Mucoadhesive Properties of Repaglinide-Loaded Nanoparticles: Mathematical Modelling through Machine Learning-Based Approach

This research work aims to develop a modified repaglinide-loaded chitosan-ethyl cellulose nanoparticles (RPG-ECSNPs) as a novel sustained-release dosage form with improved mucoadhesive properties using an emulsification solvent-evaporation technique. The RPG-ECSNPs with different particle sizes were prepared from various polymers containing ethyl cellulose (EC) as the internal phase and chitosan (CS) as the external phase, and the use of surfactants, including Tween 80 and poloxamer 188 as emulsifiers. In vitro drug release, drug loading amount, and entrapment efficiency have been influenced by changes in the concentrations of CS and EC. The mean droplet size and zeta potential of RPG-ECSNPs were 213 ± 8.5 nm and 16.4 ± 2.4 mV, respectively. The optimized formulation's entrapment efficiency was 66 ± 2.3%, and drug loading was 7.9 ± 1.65%. The release profile was significantly higher in PBS (90%) than in diluted hydrochloric acid (30%) during 24 h of the study. The mucoadhesive function of the particles was examined in vitro using part of rat intestines. The highest adhesive % was observed for the chitosan-coated NPs. No adhesive properties were noticed for chitosan-free NPs (P-value > 0.05). This indicated that ECSNPs can be successfully utilized for sustained and controlled drug delivery of RPG through the GIT.

Past Work Done on the Matrix Tablets: A Quick Reference for the Research Beginner in Sustained-release Dosage Forms

Past Work Done on the Matrix Tablets: A Quick Reference for the Research Beginner in Sustained-release Dosage Forms

The cytisine-enriched poly(3-hydroxybutyrate) fibers for sustained-release dosage form

The polymeric cytisine-enriched fibers based on poly(3-hydroxybutyrate) were obtained using electrospinning method. The biocompatibility study, advanced thermal analysis and release of cytisine from the poly(3-hydroxybutyrate) fibers were carried out. The nanofibers' morphology was evaluated by scanning electron microscopy. The formation and description of phases during the thermal processes of fibers by the advanced thermal analysis were examined. The new quantitative thermal analysis of polymeric fibers with cytisine phases based on vibrational, solid and liquid heat capacities was presented. The apparent heat capacity of fibers was measured using the standard differential scanning calorimetry. The quantitative analysis allowed for the study of the glass transition and melting/crystallization process. The mobile amorphous fraction, degree of crystallinity and rigid amorphous fraction were determined depending on the thermal history of semicrystalline polymeric fibers. Furthermore, the cytisine dissolution behaviour was studied. It was observed that the kinetic of the release from polymeric nanofiber is delayed than for the marketed product. The immunosafety of the tested polymeric nanofibers with cytisine was confirmed by the Food and Drug Agency Guidance as well as the European Medicines Agency. The polymeric matrix with cytisine seems to be a promising candidate for the prolonged release formulation.

Formulation and Evaluation of Novel Aceclofenac Matrix Tablet Using Natural Polymers

The current study attempted to design and create Aceclofenac sustained release matrix tablets employing different proportions of Hibiscus rosa-sinensis mucilage, Mimosa Pudica mucilage as natural polymers and povidone.Aceclofenac is widely used as a centrally acting muscle relaxant; therefore, have been selected to prepare sustained release dosage forms.Different types of evaluation parameters were evaluated like appearance, thickness, diameter, weight variation, hardness, friability, drug content, in-vitro dissolution studiesand stability studies.Sustained release matrix tablets can improve patient compliance by lowering the total dose and dosing schedule, which can be extremely beneficial in the treatment of chronic illnesses.
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Formulation design and optimization of sustained release tablet dosage form of Diacerein

Diacerein is both an anti-inflammatory drug and an anti-arthritic agent. At present, no sustained release dosage form of Diacerein is commercially available. The aim of the study was to develop an optimized formulation of sustained release tablet dosage form of Diacerein that will be highly patient compliant. A three-level full factorial design was employed to develop nine different formulations of matrix tablets using a combination of Methocel K100M CR and Methocel K4M CR polymer at different ratios. The physical evaluation of both the drug-excipient powder mixtures and tablets of the nine formulations were performed and results were found to be within acceptable ranges for all tests. Dissolution profiles of tablets were obtained and the kinetics of drug release from the matrix tablets were determined by employing various mathematical models. The release data were simulated in Design Expert Software to carry out statistical analysis and the effect of both polymers on release patterns were observed after 1, 4 and 8 h in terms of contour plots and 3D surface plots, which were found to be statistically significant (p < 0.05). Finally, the overlay plot was obtained from which the optimized formulation of Diacerein was determined.

Formulation and Characterization of Montelukast Sodium Mouth Dissolving Film Using Cress Seed Mucilage

There is a rising interest in the development of orodispersible films (ODFs) as an alternative to fast dissolving tablets which is attributed to their faster dissolution rate, higher durability, and better patient compliance. Owing to its rheological and also various functional properties, many researchers tried to discover some of the pharmaceutical applications of L. sativum in the development of various dosage forms, in addition to its therapeutic studies, such as binding, dissolving, gelling and sustained release dosage form. The fast-dissolving oral film of the Montelukast sodium by using Cress seed mucilage (CSM) and HPMC (15cps) is prepared by solvent casting method. The fast-dissolving oral film evaluated for folding endurance, surface pH, in-vitro disintegration time, drug content and in-vitro drug release. The physical appearance and folding endurance properties were found to be reasonably good and electron microscopy shows that films are clear, colorless with smooth surface.The drug content of all the films was in the range suggesting that drug was uniformly dispersed throughout all films. The present study was an attempt to develop and evaluate an oral fast dissolving drug delivery system using cress seed mucilage as a film former.&#x0D; Keywords: Orodispersible film, Montelukast sodium, Cress seed mucilage, HPMC

Review: Therapetic Approach in the Management of Osteoarthritis

Objectives: The goal in designing sustained or controlled delivery systems is to reduce the frequency of dosing or to increase the effectiveness of the drug by localization at the site of action, reducing the dose required, and providing uniform drug delivery. A sustained release system is a type of modified drug delivery system that can be used as an alternative to a conventional drug delivery system.&#x0D; Summary: Osteoarthritis is a generative disease of synovial joints characterized by focal loss of articular hyaline cartilage with the proliferation of new bones and remodelling of joint contour. Risk factors of osteoarthritis are age, female gender, joint alignment, hereditary gene defect, joint injury and obesity.There are various symptoms of osteoarthritis and It diagnose by blood test, joint fluid test and MRI. Osteoarthritis is treated by self-care, medications, therapies, and surgeries. A sustained-release dosage form is a dosage form that maintains the therapeutic blood or tissue levels of the drug by continuous release of medication. Formulation of granules by wet granulation and the granules are evaluated by the pre-compression and post-compression studies.&#x0D; Conclusion: Sustained release tablet optimize drug release for extended time period.It maximized effectiveness, reduced side-effects of drug and cures the disease.&#x0D;

PREPARATION AND EVALUATION OF ONCE-DAILY FLOATING GMO-ALGINATE MICROSPHERES CONTAINING FAMOTIDINE

Objective: In this work, a gastro-retentive floating microsphere delivery system composed of Drug/Glyceryl mono-oleate (GMO) embedded in a Ca-alginate gas-generated matrix was designed to improve the bioavailability of a slightly-soluble model drug Famotidine. Methods: The water/Oil emulsion method was used to prepare Famotidine floatable microspheres, and formulation variables such as Alginate: GMO ratio, gas-generated bicarbonates concentration, and loading drug concentration were investigated. Conventional techniques, including DSC, XRD and FTIR were performed to confirm Famotidine compatibility with GMO and Alginate polymers. Real-Time X-ray Radiography was used for in vivo imaging of Famotidine floatable microspheres using rabbits as an animal model. HPLC spectroscopic technique was used to determine Famotidine plasma concentration after oral administration of Alginate-GMO loaded microspheres. Results: Floating Famotidine Alginate-GMO microspheres (0.75:1:0.25) w/w/w showed a remarkable entrapment efficiency (&gt;98%), good buoyancy (&gt;84) and prolonged in vitro drug release properties (&gt;24 hours). DSC, XRD, and FTIR techniques showed no evidence of interaction between Famotidine and Alginate or GMO. In vivo Imaging of Famotidine floatable microspheres showed that capsules containing Famotidine-Alginate microspheres were not detected after 3 h of administration, while capsules containing Famotidine-GMO-Alginate microspheres can be detected for more than 12 h, indicating superior gastric retention properties. The pharmacokinetic parameters were calculated for Famotidine: GMO-Alginate, and Famotidine: alginate and compared with the plain drug over 24 h period. Famotidine: GMO-Alginate microspheres exhibited controlled and prolonged absorption Tmax of 6.0 vs. 3.0 and 2.0 h; Cmax of 124.9±0.9 vs. 323.7±0.4and 458.6±0.5 ng/ml; AUC0-24 of 2153.025±6.7 vs. 1650.4±1.9 and 1110.725±2.1 ng/ml for Famotidine: alginate and plain drug, respectively, reflecting the increase in the bioavailability of the drug in the floating formulations compared to the free drug. Conclusion: Prolonged gastric retention time and sustained release properties of floating GMO-alginate microsphere suggest that it could provide a valuable sustained release dosage form of slightly-soluble drugs.

Novel Approaches of Polyherbal Matrix Tablet and its Evaluation Parameters

According to WHO, approximately 80 percent of people in developing countries still rely on traditional medicine, which is based primarily on plant and animal species, for primary health care. Because of the toxicity and side effects of allopathic drugs, herbal therapy is becoming more popular. Medicinal plants are crucial in the development of powerful therapeutic agents. Natural products derived from plants, animals, and minerals have long been used to treat human disease Plant medicines are frequently used in combination rather than alone to maximise the benefit of their combined strength. Because of synergism, polyherbalism provides a variety of benefits not found in single herbal formulations. Polymers are the building blocks of a pharmaceutical drug delivery system because they control drug release from the device. Polymers are used to protect drugs from the physiological environment and to extend their release time in order to improve their stability. This review focuses on matrix tablets, which are one of the most practical methods for developing sustained-release dosage forms, as well as the approaches used in their formulation and evaluation. The therapeutic efficacy of a sustained release matrix tablet with improved efficacy can be increased. It also emphasizes the significance of polyherbalism and matrix Tablet.

Eudragit RS/RL을 이용한 고체분산에 의한 티카그렐러 서방형 제형 설계

티카그렐러는 급성관상동맥증후군 환자의 뇌졸중과 심장마비를 예방하는 약물로서 용해도와 생체막 투과성이 낮은 생물약제학적 분류체계 IV에 속하는 약물이다. 이에 생체이용률을 높이기 위해서는 약물가용화 과정이 필수적이다. 이를 위해 친수성이고 pH 비의존적 고분자 Eudragit RL PO, Eudragit RS PO을 사용해 분무건조법으로 습식과립공정을 통해 고체 분산체를 제조하였다. 약물이 무정형으로 고분자 매트릭스에 분산되었는지 X-ray diffractometer, differential scanning calorimetry를 통해 결정성 및 포접을 확인하였고, Fourier transform infrared spectroscopy을 통해 화학적 변화를 확인하였다. 최종적으로, 용출시험을 통해 약물의 방출제어가 잘 이루어졌는지 확인하여, 복용 회수를 줄이고 환자의 복약 순응도를 높인 제형으로 개발 가능함을 확인하였다.

Method of Starch Acetylation and Use of Acetylated Starch as Polymer in Pharmaceutical Formulations

Starch is used as a key polymer in pharmaceutical industries since long back for various purposes such as binder, disintegrating agent, bulking agent, film former and many more. But as per the purpose of dosage forms it’s used get changed. Currently scientists are more focused on controlled and sustained release dosage forms. Since, native starch does not meet up the demand of controlled or sustained release, so there is need of modifying the polymer as per dosage form requirement. Modification of starch can be done by physical, chemical, enzymatic, and genetic method. Among all, the current article is focusing on chemical modification of starch, especially the acetylation. Acetylation of starch can be done using different acetylating agent such as acetic anhydride (AA), and glacial acetic acid etc. and sodium hydroxide (NaOH), pyridine and sulphuric acid etc as a catalyst. The native structure of starch can be less efficient, since its functional properties are less stable to process condition such as high temperature, shear stress and exposure to acidic media, which decreases its use in industrial application. Acetylated starches facilitate higher stability and resistance to retrogradation or crystallization, enhanced granular size, swelling power, and water absorption capacity, which provides good flow and compression properties. It reduces the pasting temperature and solubility. It makes the acetylated starch as a good candidate for customizing the overall performance of native starch, which may be used as the controlled release or sustained release polymer in pharmaceutical dosage form.