Release Metformin Research Articles

Multifunctional mesoporous nanoselenium delivery of metformin breaks the vicious cycle of neuroinflammation and ROS, promotes microglia regulation and alleviates Alzheimer's disease

Clinical trials based on a single molecular target continue to fail, and the adverse effects of Aβ protein aggregation and neuroinflammation need to be solved and treatment of Alzheimer's disease. Herein, by designed a nano-sized flower mesoporous selenium transport carrier (Met@MSe@Tf) with high enzyme-like activity, metformin (Met) was loaded, and transferrin (Tf) was modified to bind to transferrin receptor to promote receptor-mediated transport across the BBB. In the AD lesion environment, with the acidic environment response dissociation, promote the release of metformin by nanoflower to achieve therapeutic effect in the brain lesion site. Metformin, a major anti-diabetic drug in diabetic metabolism, has been found to be a promising new therapeutic target in neurodegenerative diseases. Further studies showed that the metformin drug release from the designed and synthesized transport nanoparticles showed high intrinsic activity and the ability to degrade the substrate involved, especially the degradation of Aβ deposition in the cortex and hippocampus, increased the phagocytosis of microglia, thus relieving neuroinflammation simultaneously. Collectively, in vivo experiments demonstrated that Met@MSe@Tf significantly increased the number of NeuN-positive neurons in the hippocampus of AD mice, promoted neurovascular normalization in the brain, and improved cognitive dysfunction in AD transgenic AD mice. Thus, it provides a preclinical proof of concept for the construction of a highly modular accurate drug delivery platform for Alzheimer's disease.

Engineering 3D Printed Gummies Loaded with Metformin for Paediatric Use.

In today's pharmaceutical landscape, there's an urgent need to develop new drug delivery systems that are appealing and effective in ensuring therapeutic adherence, particularly among paediatric patients. The advent of 3D printing in medicine is revolutionizing this space by enabling the creation of precise, customizable, and visually appealing dosage forms. In this study, we produced 250 mg metformin paediatric gummies based on the semi-solid extrusion (SSE) 3D printing technique. A pharmaceutical ink containing metformin was successfully formulated with optimal flow properties suitable for room-temperature printing. Using a quality by design approach, 3D printing and casting methodologies were compared. The 3D-printed gummies exhibited better firmness and sustained release at earlier times to avoid metformin release in the oral cavity and ensure palatability. The texture and physical appearance match those of gummies commercially available. In conclusion, SSE allowed for the successful manufacture of 3D-printed sugar-free gummies for the treatment of diabetes mellitus for paediatric patients and is an easily translatable approach to clinical practice.

Preparation and Characterization of Zein-Metformin/Gelatin Nanofibers by Coaxial Electrospinning.

Metformin is a drug commonly used for the treatment of type 2 diabetes. However, it has been associated with damaging side effects when used over a long period of time. A potential solution to this problem is the implementation of a prolonged-release system for metformin, which would enhance the efficiency of the doses administered to patients. To achieve this, it is necessary to use materials compatible with humans. Electrospinning is an efficient technique that can be employed for this purpose, utilizing solvents that are safe for human use. Therefore, the objective of this study was to prepare and characterize a system for the prolonged release of metformin from zein and gelatin through coaxial electrospinning as well as to investigate its in vitro release. Metformin-loaded zein/gelatin coaxial nanofibers were prepared using the coaxial electrospinning technique and then characterized by morphological, structural, and thermal analysis. Morphologically, metformin-loaded zein/gelatin coaxial nanofibers were obtained with an average diameter of 322.6 ± 44.5 nm and a smooth surface. Fourier transform infrared spectroscopy (FTIR) analysis showed band shifts at a higher wavenumber due to drug-protein interactions by hydrogen bonding between N-H and C=O groups. Thermal gravimetric analysis (TGA) results suggested a possible interaction between materials due to an increase in the degradation temperatures of zein and gelatin when metformin was included. The transition of the crystallinity of metformin to the amorphous form was also confirmed by differential scanning calorimetry (DSC). Coaxial nanofibers exhibited an encapsulation efficiency of 66% and a profile release that showed an initial release of metformin (40%) in the first hour, followed by a gradual release until it reached equilibrium at 60 h and a cumulative release of 97% of metformin. It was concluded that using the coaxial electrospinning technique, it is possible to obtain nanofibers from polymeric solutions of zein and gelatin to encapsulate metformin, with a potential application as a prolonged-release system.

Efficacy of pegylated Graphene oxide quantum dots as a nanoconjugate sustained release metformin delivery system in in vitro insulin resistance model.

Metformin, the primary therapy for type 2 diabetes mellitus (T2DM), showed limitations such as varying absorption, rapid system clearance, required large amount, resistance, longstanding side effects. Use of Nano formulations for pharmaceuticals is emerging as a viable technique to reduce negative consequences of drug, while simultaneously attaining precise release and targeted distribution. This study developed a Polyethylene Glycol conjugated Graphene Oxide Quantum dots (GOQD-PEG) nanocomposite for the sustained release of metformin. Herein, we evaluated the effectiveness of metformin-loaded nanoconjugate in in vitro insulin resistance model. Results demonstrated drug loaded nanoconjugate successfully restored glucose uptake and reversed insulin resistance in in vitro conditions at reduced dosage compared to free metformin.

Localized delivery of metformin via 3D printed GelMA-Nanoclay hydrogel scaffold for enhanced treatment of diabetic bone defects

BackgroundDiabetic bone defects present significant challenges for individuals with diabetes. While metformin has been explored for bone regeneration via local delivery, its application in treating diabetic bone defects remains under-explored. In this study, we aim to leverage 3D printing technology to fabricate a GelMA-Nanoclay hydrogel scaffold loaded with metformin specifically for this purpose. The objective is to assess whether the in situ release of metformin can effectively enhance osteogenesis, angiogenesis, and immunomodulation in the context of diabetic bone defects. Materials and methodsUtilizing 3D printing technology, we constructed a GelMA-Nanoclay-Metformin hydrogel scaffold with optimal physical properties and biocompatibility. The osteogenic, angiogenic, and immunomodulatory characteristics of the hydrogel scaffold were thoroughly investigated through both in vitro and in vivo experiments. ResultsGelMA10%-Nanoclay8%-Metformin5mg/mL was selected as the bioink for 3D printing due to its favorable swelling rate, degradation rate, mechanical strength, and drug release rate. Through in vitro investigations, the hydrogel scaffold extract, enriched with metformin, demonstrated a substantial enhancement in the proliferation and migration of BMSCs within a high-glucose microenvironment. It effectively enhances osteogenesis, angiogenesis, and immunomodulation. In vivo experimental outcomes further underscored the efficacy of the metformin-loaded GelMA-Nanoclay hydrogel scaffold in promoting superior bone regeneration within diabetic bone defects. ConclusionsIn conclusion, while previous studies have explored local delivery of metformin for bone regeneration, our research is pioneering in its application to diabetic bone defects using a 3D printed GelMA-Nanoclay hydrogel scaffold. This localized delivery approach demonstrates significant potential for enhancing bone regeneration in diabetic patients, offering a novel approach for treating diabetic bone defects. The translational potential of this articleOur study demonstrates, for the first time, the successful loading of the systemic antidiabetic drug metformin onto a hydrogel scaffold for localized delivery. This approach exhibits significant efficacy in mending diabetic bone defects, presenting a promising new avenue for the treatment of such conditions.

Microalgae‐Based Dual Drug Delivery System with Enhanced Articular Cavity Retention for Osteoarthritis Treatment

AbstractOsteoarthritis (OA) is a prevalent degenerative joint disease globally, and the availability of effective treatments for OA remains limited. Recent research has shown that metformin offers pleiotropic advantages in the development of OA. However, the therapeutic effects of metformin are hindered by inadequate residence time within the joints, instability, and low bioavailability. In this study, the utilization of natural microalgae S. platensis (SP) is proposed as carriers for metformin, resulting in the development of a metformin delivery system (SP@Met) as a dual drug delivery system that exhibits responsive dual drug cascade release and improved retention within the articular cavity. The local administration of SP@Met has demonstrated efficacy in extending the drug retention time within the articular cavity, while also enabling cascade release of both metformin and phycocyanin. SP@Met can effectively eliminate reactive oxygen species, reduce the expression of pro‐inflammatory cytokines, and restore the balance of cartilage anabolism and catabolism, thereby impeding the progression of OA. This therapeutic approach utilizes a natural microalgae carrier to facilitate efficient delivery of metformin to the articular cavity, resulting in synergistic therapeutic efficacy and offering a promising avenue for the management of OA for potential clinical application.

A Better Method for Pharmaceutical Quality Control for Impurity Profile Data

The objective of present investigation was to design the concept of hydro dynamically balanced bilayered tablet containing glimepiride and pioglitazone hydrochloride as immediate release layer and metformin hydrochloride as sustain release floating layer. Floating layer of metformin hydrochloride was prepared by employing different grades of gel forming agent and by various gas generating agent. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, in vitro buoyancy, swelling index and dissolution studies. The prepared tablets exhibited satisfactory physico-chemical characteristics. All the prepared batches showed good in vitro buoyancy. The tablet swelled radially and axially during in vitro buoyancy studies. It was observed that the tablet remained buoyant for 12 hours. The drug release from the tablets was sufficiently sustained.

Changes in lipid profile in patients with type 2 diabetes labeled as metformin-intolerant rechallenged with extended release metformin

Changes in lipid profile in patients with type 2 diabetes labeled as metformin-intolerant rechallenged with extended release metformin

Improvement of cardiovascular risk estimated by the SCORE2-Diabetes calculator in patients with type 2 diabetes treated with extended release metformin

Improvement of cardiovascular risk estimated by the SCORE2-Diabetes calculator in patients with type 2 diabetes treated with extended release metformin

Ternary Blend of Chitosan/Polyvinyl Alcohol/Carboxymethylcellulose as an Efficient System for the Release Studies of Metformin Hydrochloride

AbstractChitosan (CS) has attracted substantial attention as a sustainable biopolymer in drug delivery applications, in recent years, because of its nontoxicity, biocompatibility, and accessibility. This study develops chitosan/polyvinyl alcohol/carboxymethylcellulose (CS/PVA/CMC) ternary hydrogel with excellent efficacy as a potential delivery vehicle for the antidiabetic drug metformin hydrochloride. The incorporation of carboxymethylcellulose (CMC) in the blend remarkably improves the swelling properties of the hydrogel. Metformin hydrochloride is loaded in the CS/PVA/CMC ternary blend by ultrasonication method. The prepared hydrogel beads are characterized by, Fourier‐transform infrared spectroscopy (FT‐IR), Scanning electron microscopy (SEM), and X‐ray diffraction (XRD) techniques and confirm the presence of the drug in the beads. The loading and release of metformin from the CS/PVA/CMC hydrogel beads are followed by UV–visible spectroscopy at 233 nm. Different formulations are prepared by varying the compositions of chitosan and carboxymethylcellulose. α‐Glucosidase inhibitory studies reveal that metformin loaded CS/PVA/CMC hydrogel beads show excellent antidiabetic activity. The maximum value of inhibitory activity observed is 89%. Cytotoxic analysis proves that the beads prepared are nontoxic.

Application of the variability budget approach to the Dissolution test

The aim. This study aimed to evaluate the completeness of our knowledge about the sources of variation in the Dissolution test with 100 % release by compiling a variability budget.
 Materials and methods. The study was performed on 500 mg metformin tablets, using pharmacopoeial quality reagents, State Pharmacopoeia of Ukraine (SPhU) Metformin HCl reference standard, Pharmatest DT70 Dissolution apparatus, Perkin Elmer Lambda 35 spectrophotometer, Mettler Toledo XP 204 analytical balance, and ISO class A volumetric glassware. The SPhU metrological approach was employed.
 Results and discussion. The variability budget was compiled based on the comparison of uncertainty estimates obtained from the requirements for maximum permissible variation in normal analytical practice (UNAP, bottom-up estimation) and experimental data (Uexp). This involved characterizing Metformin content in tablets using the Uniformity of Dosage Units (UDU) test as an independent method. The 100 % release of Metformin in the Dissolution test (infinity point) was proved by increasing the dissolution time. Having optimized Dissolution and UDU analytical procedures for variability budget compiling, we achieved insignificance of Uexp compared to the target uncertainty (Utg) for the Dissolution test in compliance testing. The differences in UDU and Dissolution mean results did not exceed UNAP for the release time of 45 and 60 min, i.e. uncertainty budget was proven. Uexp for the Dissolution test indicated the presence of an unknown statistically significant source of random variation, which, however, was less than Utg; therefore, the procedure is suitable for compliance testing.
 Conclusion. Experimental results confirmed the completeness of our knowledge about sources of variation (absence of bias) for the Dissolution test with 100 % release. An essential condition for compiling the budget was the optimization of uncertainty of analytical procedures. For UDU, all significant sources of variation were within the expected range. Yet, there is a need for additional research to identify and manage an unknown source of practically significant random variation for the Dissolution test

Separable Microneedle for Integrated Hyperglycemia Sensing and Photothermal Responsive Metformin Release.

Microdevices that offer hyperglycemia monitoring and controllable drug delivery are urgently needed for daily diabetes management. Herein, a theranostic separable double-layer microneedle (DLMN) patch consisting of a swellable GelMA supporting base layer for glycemia sensing and a phase-change material (PCM) arrowhead layer for hyperglycemia regulation has been fabricated. The Cu-TCPP(Fe)/glucose oxidase composite and 3,3',5,5'-tetramethylbenzidine coembedded in the supporting base layer permit a visible color shift at the base surface in the presence of glucose via a cascade reaction, allowing for the in situ detection of glucose in interstitial fluid. The PCM arrowhead layer is encapsulated with water monodispersity melanin nanoparticles from Sepia officinalis and metformin that is imparted with a near-infrared ray photothermal response feature, which is beneficial to the controllable release of metformin for suppression of hyperglycemia. By applying the DLMN patch to the streptozotocin-induced type 2 diabetic Sprague-Dawley rat model, the results demonstrated that it can effectively extract dermal interstitial fluid, read out glucose levels, and regulate hyperglycemia. This DLMN-integrated portable colorimetric sensor and self-regulated glucose level hold great promise for daily diabetes management.

Lubricating MXenzyme-based hybrid hydrogel reverses oxidative damage to alleviate osteoarthritis

Osteoarthritis (OA) is a lubrication-deficient joint disease accompanied by persistent inflammation and progressive destruction of articular cartilage. Although the exact pathogenesis is still unclear, oxidative stress-induced metabolic imbalance and chondrocyte death are thought to take on a crucial role. Here, we present an injectable hydrogel drug delivery system based on V2C MXenzyme NS, metformin and DexMA to alleviate the progression of OA. Due to the advantageous properties of MXenzyme, MXenzyme hybrid hydrogel not only enabled the intelligent release of metformin in response to pH, but also formed a lubricant layer on the hydrogel surface for stable boundary lubrication. Moreover, MXenzyme hybrid hydrogel could scavenge excess reactive oxygen species (ROS) in chondrocytes, including H2O2 and O2−, to alleviate oxidative stress and protect mitochondrial function. Most notably, MXenzyme Hybrid Hydrogel also maintained cartilage extracellular matrix metabolic homeostasis and inhibited chondrocyte pyroptosis through activating Nrf2-ARE signaling, thereby protected cartilage tissues and mitigated the progression of OA. Collectively, the MXenzyme hybrid hydrogel is a promising nano-delivery system for the treatment of OA.

Chitosan based hybrid superabsorbent for controlled drug delivery application.

In the present study, a hybrid chitosan-alginate superabsorbent is prepared using maleic acid as a cross-linker and acrylamide as a grafting agent using the free radical mechanism. The composite hydrogel shows good swelling capacity along with hemocompatibility and biocompatibility and hence it is utilized as a drug delivery device. The characterization techniques including x-ray diffraction, Fourier transform infrared, x-ray photoelectron spectroscopy, and thermal analysis indicate the successful synthesis of stable hydrogel with rich functionalities. Metformin hydrochloride is used as a model drug which is used to treat diabetes. The drug encapsulation is done using the swelling diffusion method after the synthesis of hydrogel. The release of metformin from the drug-loaded hydrogel at physiological pH highlights the role of non-covalent interactions between the drug and hydrogel. In vitro release studies of Metformin from the drug-loaded hydrogel show higher release profiles at intestinal pH (7.4) compared to stomach pH (1.2). The observed cumulative release is 82.71% at pH 7.4 and 45.67% at pH 1.2 after 10 h. Brunauer-Emmett-Teller analysis reveals the effect of surface area, pore size, and pore volume of hydrogel on the drug release. The drug release from the hybrid chitosan-alginate hydrogel is found to be more sustained in comparison to the pure chitosan hydrogel. For the present drug delivery system, the swelling-controlled release is found to be more dominating than the pH-controlled release. The synthesized hydrogel can be successfully employed as a potential drug delivery system for controlled drug delivery.

Engineered, Radially Aligned, Gradient-Metformin-Eluting Nanofiber Dressings Accelerate Burn-Wound Healing.

Deep, second- and third-degree burn injuries may lead to irreversible damage to the traumatized tissue and to coagulation or thrombosis of the microvessels, further compromising wound healing. Engineered, morphologically gradient drug-eluting nanofiber dressings promote wound healing by mimicking tissue structure and providing sustained drug delivery, which is particularly beneficial for wound management. This study exploited a resorbable, radially aligned nanofiber dressing that provides the sustained gradient release of metformin at the wound site using a pin-ring electrospinning technique and a differential membrane-thickness approach. The experimental results suggested that the electrospun nanofibrous dressings exhibited uniform and radially oriented fiber distributions. In vitro, these dressings offered an extended release of metformin for 30 d. The incorporation of water-soluble metformin significantly enhanced the hydrophilicity of the nanofiber membranes. Moreover, the in vivo burn-wound-healing model of rats showed that the radially aligned gradient metformin-eluting poly(lactic-co-glycolic acid) (PLGA) nanofibers exhibited significantly superior healing capability compared to the pristine PLGA, metformin-eluting, and control dressings. Histological images showed that the mesh/nanofibers produced no adverse effects. The findings in this study emphasize the potential of resorbable, radially aligned nanofiber dressings as advanced wound care solutions, offering broad applicability and meaningful clinical impact.

Multifunctional nanocomposites mediated novel hydrogel for diabetic wound repair.

The regeneration and repair of diabetic wounds, especially those including bacterial infection, have always been difficult and challenging using current treatment. Herein, an effective strategy is reported for constructing glucose-responsive functional hydrogels using nanocomposites as nodes. In fact, tannic acid (TA)-modified ceria nanocomposites (CNPs) and a zinc metal-organic framework (ZIF-8) were employed as nodes. Subsequent crosslinking with 3-acrylamidophenylboronic acid achieved functional nanocomposite-hydrogels (TA@CN gel, TA@ZMG gel) by radical-mediated polymerization. Compared with a simple physically mixed hydrogel system, the mechanical properties of TA@CN gel and TA@ZMG gel are significantly enhanced due to the intervention of the nanocomposite nodes. In addition, this kind of nanocomposite hydrogel can realize the programmed loading of drugs and release of drugs in response to glucose/PH, to coordinate and promote its application in the regeneration and repair of diabetic wounds and infected diabetic wounds. Specifically, TA@CN gel can remove reactive oxygen species and generate oxygen through its various enzymatic activities. At the same time, it can effectively promote neovascularization, thus promoting the regeneration and repair of diabetic wounds. Furthermore, glucose oxidase-loaded TA@ZMG gel exhibits glucose response and pH-regulating functions, triggering programmed metformin (Met) release by degrading the metal-organic framework (MOF) backbone. It also exhibited additional synergistic effects of antibacterial activity, hair regeneration and systemic blood glucose regulation, which make it suitable for the repair of more complex infected diabetic wounds. Overall, this novel nanocomposite-mediated hydrogel holds great potential as a biomaterial for the healing of chronic diabetic wounds, opening up new avenues for further biomedical applications.

Development of a multi-component gastroretentive expandable drug delivery system (GREDDS) for personalized administration of metformin

ABSTRACT Objectives Efficacy and compliance of type II diabetes treatment would greatly benefit from dosage forms providing controlled release of metformin in the upper gastrointestinal tract. In this respect, the feasibility of a new system ensuring stomach-retention and personalized release of this drug at its absorption window for multiple days was investigated. Methods The system proposed comprised of a drug-containing core and a viscoelastic umbrella-like skeleton, which were manufactured by melt-casting and 3D printing. Prototypes, alone or upon assembly and insertion into commercially-available capsules, were characterized for key parameters: thermo-mechanical properties, accelerated stability, degradation, drug release, deployment performance, and resistance to simulated gastric contractions. Results Each part of the system was successfully manufactured using purposely-selected materials and the performance of final prototypes matched the desired one. This included: i) easy folding of the skeleton against the core in the collapsed administered shape, ii) rapid recovery of the cumbersome configuration at the target site, even upon storage, and iii) prolonged release of metformin. Conclusions Composition, geometry, and performance of the system developed in this work were deemed acceptable for stomach-retention and prolonged as well as customizable release of metformin in its absorption window, laying promising bases for further development steps.

Controlled Release Study of Metformin Using Trithiocyanuric Acid Functionalized MCM‐41 as a Nanocarrier

AbstractOrdered nanoporous silica such as MCM‐41 has silanol groups that can be chemically modified to effectively control the release of molecules. In this regard, MCM‐41 was functionalized with trithiocyanuric acid groups (TTCA‐MCM‐41) and offered as a novel carrier to the controlled release of metformin. TTCA‐MCM‐41 was synthesized and characterized. Thereafter, for 3 hours, saturated metformin solution was contacted with TTCA‐MCM‐41 to loading of drug. Finally, drug release profile was investigated in simulated body fluid (SBF) and phosphate buffers. The hexagonal symmetry of the TTCA‐MCM‐41 was confirmed by XRD patterns. The BET surface area, centred on N2 adsorption‐desorption, dropped from 846.5 m2/g for the MCM‐41 to 295.2 m2/g for the TTCA‐MCM‐41. With the use of FT‐IR spectra, the presence of TTCA groups in the silica system was established. The rope‐shaped morphology and the existence of S and N atoms on the MCM‐41 are visible in the SEM and EDX. The metformin release from TTCA‐MCM‐41 exhibits a pH‐based behaviour, and release rate was faster at higher pH compared to lower pH in phosphate buffers. In SBF, metformin displayed a steady release rate of around 0.2 mg min−1. The findings demonstrated that TTCA‐MCM‐41 is a promising candidate as a novel metformin carrier.

Transferrin functionalized poloxamer-chitosan nanoparticles of metformin: physicochemical characterization, in-vitro, and Ex-vivo studies

Object We report the preparation, characterization, and in-vitro therapeutic evaluation of Metformin-Loaded, Transferrin-Poloxamer-Functionalized Chitosan Nanoparticles (TPMC-NPs) for their repurposing in Alzheimer’s disease (AD). Significance Usefulness of this work to establish the repurposing of metformin for the treatment of AD. Methods The TPMC-NPs were prepared by ionic gelation method using sodium tripolyphosphate. The modification and functionalization were confirmed by FTIR and 1H-NMR spectroscopy. The physicochemical characterization was performed using DLS, FTIR,1H-NMR, CD spectroscopy, SEM, DSC, PXRD, HR-TEM, and hot-stage microscopy. Results The size, PDI, percent entrapment efficiency, and percent drug loading of TPMC-NPs were found to be 287.4 ± 9.5, 0.273 ± 0.067, 81.15 ± 7.17%, 11.75%±8.21%, respectively. Electron microscope analysis revealed smooth and spherical morphology. The transferrin conjugation efficiency was found to be 46% by the BCA method. CD spectroscopy confirmed no significant loss of the secondary structure of transferrin after conjugation. PXRD data indicated the amorphous nature of the TPMC-NPs. Hot-stage microscopy and DSC confirmed the thermal stability of TPMC-NPs. The in-vitro drug release showed a sustained release at pH 7.4. The DPPH assay displayed 80% antioxidant activity of TPMC-NPs in comparison with metformin and blank NPs. The in-vitro cytotoxicity assay revealed 69.60% viable SH- SY5Y cells at 100 µg/mL of TPMC NPs. The ex-vivo nasal ciliotoxicity and mucoadhesion studies showed no significant toxicity, and 98.16% adhesion, respectively. The nasal permeability study showed the release of metformin within 30 min from TPMC-NPs. Conclusion The obtained results suggested the usefulness of TPMC-NPs in the treatment of AD via the intranasal route.

Preparation of Metformin Biodegradable Polymeric Microparticles by O/O Emulsion Solvent Evaporation: A 32 Full Factorial Design Approach

Background: Sustained release of synthetic polymeric microparticles has gained more attention as drug delivery carriers because of their properties such as good stability, low toxicity, dosing frequency, and simple and mild preparation method. The present work was envisaged to reduce the dosing frequency by preparing drug loaded biodegradable microspheres by the O/O emulsion solvent evaporation technique. Objective: The objective behind microspheres’ preparation is to sustain the metformin release by using ethyl cellulose as a synthetic polymer. The model drug metformin having a low biological half-life (1.5-3 hours) is selected. Methods: As the metformin is highly water soluble in nature, the oil-in-oil solvent evaporation techniques are used and span 80 is utilized as surfactant. The effect of stirring rate and surfactant concentration on the characteristics of encapsulation efficiency and drug release from the microsphere are investigated. Results: The results show that the drug-polymer (1:1) ratio gives better sustained release results. The obtained microparticles are characterized by X-RD analysis and Fe-SEM, and release behavior is checked for release patterns. A 32 full factorial design is employed for the responses. The free-flowing spherical microspheres show high drug entrapment efficiency. Conclusion: The data obtained suggest that microspheres can be successfully designed with sustained release for diabetic treatment.