Sustained-release Formulation Research Articles

Isolation and Characterization of Colon Targeting Starch from the Non‐Conventional Source of Jharkhand, India

AbstractStaple foods are generally the conventional sources of starch. The exploration of non‐conventional and cheap sources of starch has gained momentum. In the present study, starch from mankanda (Alocaisa macrrorhizos) tubers is isolated by using base, NaOH 0.05%, w/w sodium hydroxide extracted starch (NAS) and acidic (citric acid 0.03%; Citric acid extracted starch (CAS) media and evaluated for its physicochemical, structural, thermal, rheological, and release profile. The %yield of NAS and CAS starch is found to be 8.14% and 7.28%, with neutral pH, high water holding capacity, moisture content, amylose content, low ash values, restricted swelling, and excellent flow. The granules of the starches are irregular, with a diameter ranging from 1.34 to 16.12 µm. X‐ray diffraction (XRD) analysis reveals the combination of type A and B crystal. Fourier Transform Infrared Spectroscopy (FT‐IR) spectra of both starch samples are almost found to be similar in nature. Thermogravimetric analysis (TGA) and differential scanning colorimetric (DSC) analysis indicate good thermal stability. Both starches exhibit shear thinning behavior. In vitro drug release studies reflect that the extracted native starch from mankanda tubers has an immense potential for the development of sustained release formulations to target the lower gastrointestinal region like the colon by protecting the drug from the physiological environment of the stomach and small intestine.

Development of Novel Formulation for Sustained Release of Drug to Prevent Swainsonine-Containing Plants Poisoning in Livestock.

Swainsonine-containing plants contain swainsonine which has been shown to cause neurological signs and pathological changes in farm animals. It causes a large number of livestock poisonings every year resulting in economic losses to the livestock industry. At present, "Jifang E" is used in the prevention of swainsonine-containing plants poisoning livestock, and the preventive effects have been well-documented. However, "Jifang E" is typically administered in drinking water, making it difficult to control the administered dosage, because of feeding difficulties and it may cause certain side effects that are unique to the water-dissolved powder. To overcome these difficulties, we developed a temperature-sensitive gel for injection and the optimal ratio of each formula of sustained-release injection is P407 (24%), P188 (6%), Vitamin C (1%), PEG4000 (0.5%), and "Jifang E" (10%). Our results suggest that novel formulation makes the micellar system more stable and the particles are uniformly dispersed. Colloidal morphological studies showed that each group formed a homogeneous pore structure after gelling, and the structure became more dense with the addition of "Jifang E". The rheological study shows that "Jifang E" is a pseudoplastic fluid, and the addition of "Jifang E" reduces the viscosity of the formula, which is beneficial to the injection. In vitro and in vivo release rate studies have shown that the effective concentration of "Jifang E" can be maintained for 3 to 5 days. The acute toxicity test in SPF Kunming mice showed that its LD50 was 828.323 mg/kg, with confidence limits of 676.706-1013.911 mg/kg, which is a safe dosage (LD50 > 200 mg/kg). There were no observed reactions of muscle irritation or subcutaneous tissue irritation with the dosage used for New Zealand rabbits. In summary, we successfully developed the sustained-release injection formulation of "Jifang E" for the prevention of swainsonine-containing plants poisoning livestock, which provides the basis for subsequent field extension trials and the further study of its detoxification mechanism.

Formulation and in vitro evaluation of lamivudine loaded nanoparticles

Nanoparticles represent a promising drug delivery system of sustained and targeted drug release. They are specially designed to release the drug in the vicinity of target tissue. The aim of this study was to prepare and evaluate PLGA nanoparticles containing Lamivudine in different drug to polymer ratio. SEM indicated that nanoparticles have a discrete spherical structure. FT-IR studies indicated that there was no chemical interaction between drug and polymer and stability of drug. The in vitro release behavior from all the drug loaded batches was found to be Higuchi release and provided sustained release over a period of 12 h. The developed formulation overcome and alleviates the drawbacks and limitations of Lamivudine sustained release formulations and could possibility be advantageous in terms of increased bioavailability of Lamivudine.

Extraction, Characterization, and Evaluation of Lepidium sativum Linn. Mucilage as a Mucoadhesive Polymer.

Being biocompatible, less toxic, cheap, easily available, and environmentally friendly, there is an increased trust in natural polymers in the drug delivery system. Mucilages, among the natural polymers, are the primary metabolites of plants that have been widely utilized in pharmaceutical manufacturing for different purposes, and mucoadhesive is one among them. The present study was designed to investigate the use of LSM as a mucoadhesive polymer using ibuprofen as a model drug. The mucilage was extracted following an aqueous extraction method and its percentage yield was found to be 13.2% w/w. Besides, three microsphere formulations of ibuprofen were prepared using synthetic polymer hydroxyl propyl methyl cellulose (HPMC) K100M and the LSM in polymer to drug ratios of 1 : 1, 1 : 5, and 3 : 5 by applying ionotropic gelation followed by solvent evaporation methods. The microspheres were evaluated for various micromeritic properties and all the formulations exhibited free-flowing properties. Optical microscopic pictures of almost all the microspheres except F3 and F6 (which had more or less spherical shapes) were found to have irregular and discrete shapes. Besides, the surfaces of all the formulations were rough in texture. The drug entrapment efficiency of the microspheres was found to be between 52.08% ± 0.80 and 87.97% ± 0.72. The in-vitrowash-off test evidenced that almost 50 percent (especially F3) of the microspheres were able to adhere up to 18 h and showed remarkable bioadhesion properties. The in-vitro drug release profile indicated that all the formulations were able to prolong their drug release up to 12 h with a non-fickian release mechanism, except for F4, which followed a fickian release. Therefore, based on the findings of this study, LSM can be used as a potential alternative mucoadhesive excipient for sustained release formulations.

Thermo-responsive Diels-Alder stabilized hydrogels for ocular drug delivery of a corticosteroid and an anti-VEGF fab fragment

In the present study, a novel in situ forming thermosensitive hydrogel system was investigated as a versatile drug delivery system for ocular therapy. For this purpose, two thermosensitive ABA triblock copolymers bearing either furan or maleimide moieties were synthesized, named respectively poly(NIPAM-co-HEA/Furan)-PEG6K-P(NIPAM-co-HEA/Furan) (PNF) and poly(NIPAM-co-HEA/Maleimide)-PEG6K-P(NIPAM-co-HEA/−Maleimide) (PNM). Hydrogels were obtained upon mixing aqueous PNF and PNM solutions followed by incubation at 37 °C. The hydrogel undergoes an immediate (<1 min) sol-gel transition at 37 °C. In situ hydrogel formation at 37 °C was also observed after intravitreal injection of the formulation into an ex vivo rabbit eye. The hydrogel network formation was due to physical self-assembly of the PNIPAM blocks and a catalyst-free furan-maleimide Diels−Alder (DA) chemical crosslinking in the hydrophobic domains of the polymer network. Rheological studies demonstrated sol-gel transition at 23 °C, and DA crosslinks were formed in time within 60 min by increasing the temperature from 4 to 37 °C. When incubated at 37 °C, these hydrogels were stable for at least one year in phosphate buffer of pH 7.4. However, the gels degraded at basic pH 10 and 11 after 13 and 3 days, respectively, due to hydrolysis of ester bonds in the crosslinks of the hydrogel network. The hydrogel was loaded with an anti-VEGF antibody fragment (FAB; 48.4 kDa) or with corticosteroid dexamethasone (dex) by dissolving (FAB) or dispersing (DEX) in the hydrogel precursor solution. The FAB fragment in unmodified form was quantitatively released over 13 days after an initial burst release of 46, 45 and 28 % of the loading for the 5, 10 and 20 wt% hydrogel, respectively, due to gel dehydration during formation. The low molecular weight drug dexamethasone was almost quantitively released in 35 days. The slower release of dexamethasone compared to the FAB fragment can likely be explained by the solubilization of this hydrophobic drug in the hydrophobic domains of the gel. The thermosensitive gels showed good cytocompatibility when brought in contact with macrophage-like mural cells (RAW 264.7) and human retinal pigment epithelium-derived (ARPE-19) cells. This study demonstrates that PNF-PNM thermogel may be a suitable formulation for sustained release of bioactive agents into the eye for treating posterior segment eye diseases.

Beneficial roles of sustained release formulations of diacerein microspheres in comparison to free diacerein incomplete Freund's adjuvant (C.F.A.) induced arthritis model in rat

Beneficial roles of sustained release formulations of diacerein microspheres in comparison to free diacerein incomplete Freund's adjuvant (C.F.A.) induced arthritis model in rat

Integration of artificial neural network and physiologically based biopharmaceutic models in the development of sustained-release formulations.

Model-informed drug development is an important area recognized by regulatory authorities and is gaining increasing interest from the generic drug industry. Physiologically based biopharmaceutics modeling (PBBM) is a valuable tool to support drug development and bioequivalence assessments. This study aimed to utilize an artificial neural network (ANN) with a multilayer perceptron (MLP) model to develop a sustained-release matrix tablet of metformin HCl 500mg, and to test the likelihood of the prototype formulation being bioequivalent to Glucophage® XR, using PBBM modeling and virtual bioequivalence (vBE). The ANN with MLP model was used to simultaneously optimize 735 formulations to determine the optimal formulation for Glucophage® XR release. The optimized formulation was evaluated and compared to Glucophage® XR using PBBM modeling and vBE. The optimized formulation consisted of 228mg of hydroxypropyl methylcellulose (HPMC) and 151mg of PVP, and exhibited an observed release rate of 42% at 1h, 47% at 2h, 55% at 4h, and 58% at 8h. The PBBM modeling was effective in assessing the bioequivalence of two formulations of metformin, and the vBE evaluation demonstrated the utility and relevance of translational modeling for bioequivalence assessments. The study demonstrated the effectiveness of using PBBM modeling and model-informed drug development methodologies, such as ANN and MLP, to optimize drug formulations and evaluate bioequivalence. These tools can be utilized by the generic drug industry to support drug development and biopharmaceutics assessments.

Technology Transfer and Process Validation of Metformin Hydrochloride Immediate Release Tablet

Metformin Hydrochloride, inhibits the mitochondrial respiratory chain in the liver, leading to activation of AMPK, enhancing insulin sensitivity (via effects on fat metabolism) and lowering cAMP, thus reducing the expression of gluconeogenic enzymes. Metformin improves blood sugar levels by lowering the amount of glucose (sugar) that we absorb from our diet. It also helps stop the production of new glucose and improves insulin sensitivity. Metformin Hydrochloride is videly used in the form of sustained release formulation of Tablets. The study aimed to formulate and validate novel process for the Metformin Hydrochloride in immediate release pharmaceutical solid dosage forms. The wet granulation method used for formulation of Metformin Hydrochloride Immediate Release Tablets. Metformin Hydrochloride 500 mg, 850 mg, 1000 mg film coated tablets was prepared using FBE granulation technology on lab scale size. This study was carried out through a systematic plan; critical parameters were optimized to engender a stable &amp; robust manufacturing process. The result of all three batches &amp; its critical steps clearly shows consistency &amp; reproducibility of parameters and all results. Hence the manufacturing method of Metformin Hydrochloride 500 mg, 850 mg, 1000 mg Film Coated tablets are validated at above parameters &amp; equipments. Three validation batches of commercial scale batch size were taken successfully and monitored the in-process critical parameters for commercial batches. Metformin Hydrochloride tablets were manufactured within specified Limits for meeting all quality attributes and loaded for stability study. The overall successful three consecutive validation batches of Metformin Hydrochloride film coated tablets (500, 850 &amp; 1000 mg) verifies the international technology transfer success.

GastroPlus- and HSPiP-Oriented Predictive Parameters as the Basis of Valproic Acid-Loaded Mucoadhesive Cationic Nanoemulsion Gel for Improved Nose-to-Brain Delivery to Control Convulsion in Humans.

Oral and parenteral delivery routes of valproic acid (VA) are associated with serious adverse effects, high hepatic metabolism, high clearance, and low bioavailability in the brain. A GastroPlus program was used to predict in vivo performance of immediate (IR) and sustained release (SR) products in humans. HSPiP software 5.4.08 predicted excipients with maximum possible miscibility of the drug. Based on the GastroPlus and HSPiP program, various excipients were screened for experimental solubility, nanoemulsions, and respective gel studies intended for nasal-to-brain delivery. These were characterized by size, size distribution, polydispersity index, zeta potential, morphology, pH, % transmittance, drug content, and viscosity. In vitro drug release, ex vivo permeation profile (goat nasal mucosa), and penetration studies were conducted. Results showed that in vivo oral drug dissolution and absorption were predicted as 98.6 mg and 18.8 mg, respectively, from both tablets (IR and SR) at 8 h using GastroPlus. The predicted drug access to the portal vein was substantially higher in IR (115 mg) compared to SR (82.6 mg). The plasma drug concentration-time profile predicted was in good agreement with published reports. The program predicted duodenum and jejunum as the prime sites of the drug absorption and no effect of nanonization on Tmax for sustained release formulation. Hansen parameters suggested a suitable selection of excipients. The program recommended nasal-to-brain delivery of the drug using a cationic mucoadhesive nanoemulsion. The optimized CVE6 was associated with the optimal size (113 nm), low PDI (polydispersity index) (0.26), high zeta potential (+34.7 mV), high transmittance (97.8%), and high strength (0.7% w/w). In vitro release and ex vivo permeation of CVE6 were found to be substantially high as compared to anionic AVE6 and respective gels. A penetration study using confocal laser scanning microscopy (CLSM) executed high fluorescence intensity with CVE6 and CVE6-gel as compared to suspension and ANE6. This might be attributed to the electrostatic interaction existing between the mucosal membrane and nanoglobules. Thus, cationic nanoemulsions and respective mucoadhesive gels are promising strategies for the delivery of VA to the brain through intransal administration for the treatment of seizures and convulsions.

Optimizing glucocorticoid therapy for Behçet's uveitis: efficacy, adverse effects, and advances in combination approaches.

Behçet's uveitis (BU) is a debilitating manifestation of Behçet's disease, often requiring prompt and aggressive treatment to prevent vision loss. Glucocorticoids (GCS) serve as a first-line therapy for BU; however, their long-term, high-dose use can result in significant adverse effects. This review summarizes the efficacy, adverse effects, and advances in combination therapy involving GCS for the management of BU. We discuss the benefits and drawbacks of various GCS administration routes, including periocular and intravitreal injections, intravitreal sustained-release devices, and systemic therapy, highlighting the role of fluocinolone acetonide and dexamethasone as primary sustained-release formulations. Moreover, we underscore the importance of combining GCS with immunosuppressive drugs and biological agents to minimize adverse reactions and optimize therapeutic outcomes. The review concludes that, while GCS remain a crucial component of BU treatment, careful consideration of their administration and combination with other therapies is essential to achieve long-term remission and improved visual outcomes for patients with BU.

Efficacy and Anti-Inflammatory Activity of Ashwagandha Sustained-Release Formulation on Depression and Anxiety Induced by Chronic Unpredictable Stress: in vivo and in vitro Studies.

Stress is the psychological, physiological, and behavioral response of an individual's body when they perceive a lack of equilibrium between the demands placed upon them and their ability to meet those demands. Adaptogens are herbs that help with stress management, and Ashwagandha is one such safe and effective adaptogen. We evaluated the anti-neuroinflammatory potential of Ashwagandha sustained-release formulation (AshwaSR) by estimating the in vitro expression of pro-inflammatory cytokines, and its efficacy on anxiety and depression in an in vivo study. Our in vitro study investigated the anti-inflammatory potential of AshwaSR by estimating the expression of tumour necrosis factor [TNF]-α and interleukin [IL]-1β levels in LPS-induced THP-1 human monocytes, and the antioxidant effects by its potential to inhibit the superoxide [SO] generation in PMA-induced HL-60 human monocytic cells. The in vivo study assessed the efficacy of AshwaSR on chronic unpredictable stress (CUS)-induced comorbid anxiety and depression in Sprague Dawley rats. Antidepressant and anxiolytic effects of AshwaSR were evaluated by open field test (OFT), elevated plus maze (EPM), forced swim test (FST), and Morris water maze (MWM) test. AshwaSR inhibited TNF-α, IL-1β and superoxide production in a dose-dependent manner in the in vitro study. The in vivo CUS model induced depression-like and anxiety-like behaviour. Treatments with AshwaSR and escitalopram showed improvement in the EPM and MWM models compared to the CUS-group. In vitro study demonstrated that AshwaSR inhibits expressions of pro-inflammatory cytokines, IL-1β and TNF-α, and superoxide production. Further, the in vivo study confirmed its anxiolytic and stress-relieving effects in the CUS model that confirmed AshwaSR's potential in managing stress and stress-related symptoms.

A Review on Revolutionize Drug Delivery with Spansules

This article provides a brief overview of Spansules, a novel drug delivery system. Spansules are designed to release medication in a controlled manner, providing a sustained and consistent therapeutic effect. This delivery method involves encapsulating the drug in a special coating that dissolves slowly, allowing the medication to be released gradually over time. Spansules have been shown to improve patient compliance and reduce side effects associated with traditional drug delivery methods. Spansules are classified as an Advanced Drug Delivery System due to their ability to facilitate controlled and sustained release of medication over an extended duration. The delivery system in question has the capability to maintain a consistent plasma drug concentration across a broad time spectrum. This attribute can enhance the effectiveness of treatment and mitigate the likelihood of adverse reactions. Spansules can be utilized for the delivery of multiple drugs in a single dosage form, while also providing sustained release. The Spansules product offers a multi-drug regimen capability, which enables the administration of multiple drugs in a single dosage form, providing added benefits. Spansules are a type of biphasic release drug delivery system that enables the administration of medication in both immediate and sustained release forms. In situations where a patient necessitates prompt alleviation of symptoms followed by sustained management over an extended duration, these systems can prove to be advantageous. In general, Spansules represent a versatile and efficacious mechanism for drug delivery that can offer numerous advantages to both patients and healthcare providers. Overall, Spansules represent a promising advancement in the field of drug delivery.

Optimization and evaluation of Lisinopril mucoadhesive sustained release matrix pellets: In-vitro and ex-vivo studies

Lisinopril (LIS) is antihypertensive drug, classified as a class III drug with high water solubility and low permeability. To overcome the low permeability, 32 factorial designs aimed to formulate LIS as a sustained-release (LIS-SR) matrix pellet by extrusion/spheronization. Matrix pellets were composed of wet mass containing Avicel® and polymeric matrix polymers (sodium alginate (SA) and chitosan (CS)). Evaluation of the effect of two independent variables, matrix-forming units (SA and CS) on mean line torque, on pellet size, dissolution rate after 6 h, and mucoadhesion strength of the pellets were assessed using Statgraphics software. The tested formulations (F1-F9) showed that mean line torque ranged from 1.583 to 0.461 Nm, with LIS content in the LIS-SR pellets ranged from 87.9 to 103%, sizes varied from 1906 to 1404 µm and high percentages of drug released from pellets formulations (68.48 to 74.18 %), while the mean zeta potential value of mucoadhesive range from −17.5 to –22.9 mV.The selection of optimized formulation must have the following desirability: maximum peak torque, maximum pellets’ particle size, and minimum % LIS release after 6hr. LIS optimized sustained release pellet formula composed of 2,159 % SA and 0.357 % CS was chosen as optimized formula. It’s showed a 1.055 Nm mean line torque was responsible for the increased pellet size to 1830.8 μm with decreased release rate 56.2 % after 6 hr, and −20.33 mV average mucin zeta potential.Ex-vivo mucoadhesion studies revealed that that the optimize formulation, exhibited excellent mucoadhesive properties, after 1 h, about 73% of the pellets were still attached to the mucus membrane. Additionally, ex-vivo permeation determination of LIS from the optimized LIS-SR formulation was found to be significantly higher (1.7-folds) as compared to free LIS.In conclusion: LIS-SR matrix pellets, prepared with an extrusion/spheronization have desirable excellent characteristics in-vitro and ex-vivo sustained-release pellet formulation of LIS-SR was able to sustain the release of LIS for up to 8 h.

Ultimate fate, transformation, and toxicological consequences of herbicide pretilachlor to biotic components and associated environment: An overview.

Herbicides are applied for effective weed management in order to increase the crop yield. In recent decades, the overuse of these chemicals has posed adverse effects on different biotic components of the environment. Pretilachlor has been widely used during last few decades for weed management in paddy crop. Its excessive use may prove fatal for environment, various organisms, and nontarget plants. Thus, it is pertinent to know the extent to which herbicide residues remain in environment. The potential mobility and the release rate of herbicide in the soil are important factors governing ecotoxicological impact and degradation rate. Therefore, several techniques are being investigated for its effective removal from the contaminated sites. Furthermore, efforts have also been made to study the degradation of pretilachlor by various physicochemical processes, resulting into the formation of different types of metabolites. This review summarizes the available information on environmental fate, various degradation processes, microbial biotransformation, metabolites formed, ecotoxicological effects, techniques for detection in environmental samples, effect of safener, and various control release formulations for sustained release of pretilachlor in applied fields. The information so obtained will be very advantageous in deciding the future policies for safe and judicious use of the herbicide by maintaining health and environmental sustainability.

781-P: Sustained-Release Formulation Development and Preclinical Evaluations of Monthly or Bimonthly Injectable Semaglutide and Tirzepatide

Objective: Accumulated real-world data indicates strong tendencies to develop long-acting formulating drug. This study aimed for optimization and preclinical development of the sustained-release formulation of Semaglutide (PT403) and Tirzepatide (PT404) to explore whether they are applicable for bi-monthly (once every two months) injectable drugs. Methods: Semaglutide or Tirzepatide dissolved in acetic acid with diverse combination of biodegradable PLGA polymers was applied to the ultrasonic spray dryer that produces API-encapsulated microspheres. The pharmacokinetic profiles of PT403 and PT404 were tested in rats and minipigs after a single subcutaneous injection. Results: Both optimized formulation of PT403 and PT404 have demonstrated favorable physicochemical properties, showing uniformly sized microspheres (20±3 μm). Furthermore, the aggregation issue of Semaglutide, which was not observed in PT404, was solved by applying PROW technology. Also, increased encapsulation rates and higher drug loading (~8%) showed higher bioavailability, no initial burst and a short lag phase (&amp;lt;3 days). Additionally, the release of PT403 initiated from 3 days to 70 days in minipigs, which potentially indicates every two months injectable (Q8W) in humans, compared to the once-a-weekly (QW) Semaglutide and Tirzepatide. Lastly, double injection of PT403 can easily reached the therapeutic window with 1.4 of the Peak-to-Through ratio, based on simulated PK profiles in repeated injection in human. Conclusion: Evidence from recent formulation studies of PT403 and PT404 indicates that Peptron's SmartDepot technology is strongly applicable for long-acting drugs. The comprehensive results of formulation development, preclinical data, and mass production will provide the basis for successful clinical development of PT403 and PT404 as monthly or bi-monthly injectable diabetes and obesity drugs. Disclosure J.Jung: None. S.Chang: None.

Mucoadhesive 3D printed vaginal ovules to treat endometriosis and fibrotic uterine diseases

Gynaecological health is a neglected field of research that includes conditions such as endometriosis, uterine fibroids, infertility, viral and bacterial infections, and cancers. There is a clinical need to develop dosage forms for gynecological diseases that increase efficacy and reduce side effects and explore new materials with properties tailored to the vaginal mucosa and milieu. Here, we developed a 3D printed semisolid vaginal ovule containing pirfenidone, a repurposed drug candidate for endometriosis. Vaginal drug delivery allows direct targeting of the reproductive organs via the first uterine pass effect, but vaginal dosage forms can be challenging to self-administer and retain in situ for periods of more than 1–3 h. We show that a semisoft alginate-based vaginal suppository manufactured using semisolid extrusion additive manufacturing is superior to vaginal ovules made using standard excipients. The 3D-printed ovule showed a controlled release profile of pirfenidone in vitro in standard and biorelevant release tests, as well as better mucoadhesive properties ex vivo. An exposure time of 24 h of pirfenidone to a monolayer culture of an endometriotic epithelial cell line, 12Z, is necessary to reduce the cells’ metabolic activity, which demonstrates the need for a sustained release formulation of pirfenidone. 3D printing allowed us to formulate mucoadhesive polymers into a semisolid ovule with controlled release of pirfenidone. This work enables further preclinical and clinical studies into vaginally administered pirfenidone to assess its efficacy as a repurposed endometriosis treatment.

Formulation and Evaluation of New Sustained Release Floating Microspheres of Cilnidipine by Solvent-Diffusion Evaporation Technique

The purpose of the present investigation was to develop a gastro-retentive cilnidipine loaded floating microspheres. The floating microspheres of cilnidipine were prepared by the solvent evaporation method for oral drug delivery using HPMCK4M and ethyl cellulose as polymers. The drug loaded microspheres were evaluated for particle size, drug content, entrapment efficiency and floating time. The in-vitro study was performed in pH 1.2 to determine the amount of drug released. Field emission scanning electron microscopy (SEM) was performed to check the surface morphology of microspheres. The mean particle size of the microspheres was in the range of 226.85 – 339.42µm. The drug content of the floating microspheres was more than 70% and drug entrapment efficiency of microspheres obtained between 64.64 – 83.0%. The in-vitro buoyancy was more than70%. Cumulative % of drug release obtained between 73.12 – 89.68%. Field emission scanning microscopy results showed that the prepared microspheres were smooth and spherical.The study reveals that more the particle size extended the floating time, this methods reveals that the drug content of the microspheres enhanced as the amount of polymer increased or increased in ethyl cellulose concentration also leads to increase in entrapment efficiency and particle size. Cumulative % drug release decreased as ethyl cellulose concentration increased.&#x0D; Keywords: cilnidipine, microspheres, floating drug delivery system, entrapment efficiency, cumulative drug release, ethyl cellulose, Field emission scanning electron microscopy, polymer, concentration

Recent Advances in Formulations for Long-Acting Delivery of Therapeutic Peptides.

Recent preclinical and clinical studies have focused on the active area of therapeutic peptides due to their high potency, selectivity, and specificity in treating a broad range of diseases. However, therapeutic peptides suffer from multiple disadvantages, such as limited oral bioavailability, short half-life, rapid clearance from the body, and susceptibility to physiological conditions (e.g., acidic pH and enzymolysis). Therefore, high peptide dosages and dose frequencies are required for effective patient treatment. Recent innovations in pharmaceutical formulations have substantially improved therapeutic peptide administration by providing the following advantages: long-acting delivery, precise dose administration, retention of biological activity, and improvement of patient compliance. This review discusses therapeutic peptides and challenges in their delivery and explores recent peptide delivery formulations, including micro/nanoparticles (based on lipids, polymers, porous silicon, silica, and stimuli-responsive materials), (stimuli-responsive) hydrogels, particle/hydrogel composites, and (natural or synthetic) scaffolds. This review further covers the applications of these formulations for prolonged delivery and sustained release of therapeutic peptides and their impact on peptide bioactivity, loading efficiency, and (in vitro/in vivo) release parameters.

A review on in vitro model of the blood-brain barrier (BBB) based on hCMEC/D3 cells.

The establishment of in vitro models of the BBB is of great significance for the evaluation of the mechanism and permeability of drugs and their sustained-release formulations across the BBB. Among the different models, the immortalized human cell line hCMEC/D3 has the potential to be used for a standardized in vitro BBB model due to its high throughput, reproducibility, homology and low cost. The high permeability of the paracellular pathway and the low expression of both certain transporters and metabolic enzymes in this model lead to low physiological levels of physical, transport and metabolic barriers, thus limiting the application of these cells. The barrier properties of this model have been improved in different studies by various means. However, no systematic review has been conducted on the optimization of model-building conditions or on the regulation and expression of transporters in the models. Some existing reviews focus on the overall description of the entire field of blood-brain barrier in vitro models, lacking in-depth and systematic reviews on the experimental details and model evaluation methods based on hCMEC/D3.This paper deals with a detailed review on the optimization of multiple aspects and modalities of the hCMEC/D3 cell culture process, including initial medium, optimal serum levels, Transwell membrane materials, supra-membrane supports, inoculum density, endogenous growth factor, exogenous drug levels, co-culture and transfection methods, to provide references for the establishment and evaluation of hCMEC/D3 cell models.

Sustained-Release Vildagliptin 100 mg in Type 2 Diabetes Mellitus: A Review.

Dipeptidyl peptidase-4 inhibitors (DPP4Is) were introduced into the management of type 2 diabetes mellitus (T2DM) as they are insulinotropic and have no inherent risk of hypoglycemia and no effect on body weight. Currently, 11 drugs in this class are available for the management of diabetes. Although they have a similar mechanism of action, they differ from one other in their binding mechanisms, which influences their therapeutic and pharmacological profiles. Vildagliptin's overall safety and tolerability profile was comparable to placebo throughout clinical studies, and real-world data in a large group of T2DM patients corroborated this finding. Therefore, DPP4Is like vildagliptin is a secure alternative for treating patients with T2DM. Vildagliptin treatment given as a once-daily (QD) 100 mg sustained release (SR) formulation fits the criteria of adherence and compliance. This SR formulation, given once daily has the potential to provide glycemic control like the vildagliptin 50 mg twice-daily (BD) formulation. This comprehensive review discusses the journey of vildagliptin as 50 mg BD therapy as well as 100 mg SR QD therapy.