Sustained-release Formulation Research Articles

Development of Amorphous Solid Dispersion Sustained-Release Formulations with Polymer Composite Matrix-Regulated Stable Release Plateaus.

This study was designed to develop ibuprofen (IBU) sustained-release amorphous solid dispersion (ASD) using polymer composites matrix with drug release plateaus for stable release and to further reveal intrinsic links between polymer' matrix ratios and drug release behaviors. Hydrophilic polymers and hydrophobic polymers were combined to form different composite matrices in developing IBU ASD formulations by hot melt extrusion technique. The intrinsic links between the mixed polymer matrix ratio and drug dissolution behaviors was deeply clarified from the dissolution curves of hydrophilic polymers and swelling curves of composite matrices, and intermolecular forces among the components in ASDs. IBU + ammonio methacrylate copolymer type B (RSPO) + poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP VA64) physical mixtures presented unstable release behaviors with large error bars due to inhomogeneities at the micrometer level. However, IBU-RSPO-PVP VA64 ASDs showed a "dissolution plateau phenomenon", i.e., release behaviors of IBU in ASDs were unaffected by polymer ratios when PVP VA64 content was 35% ~ 50%, which could reduce risks of variations in release behaviors due to fluctuations in prescriptions/processes. The release of IBU in ASDs was simultaneously regulated by the PVP VA64-mediated "dissolution" and RSPO-PVP VA64 assembly-mediated "swelling". Radial distribution function suggested that similar intermolecular forces between RSPO and PVP VA64 were key mechanisms for the "dissolution plateau phenomenon" in ASDs at 35% ~ 50% of PVP VA64. This study provided ideas for developing ASD sustained-release formulations with stable release plateau modulated by polymer combinations, taking full advantages of simple process/prescription, ease of scale-up and favorable release behavior of ASD formulations.

Nanoemulsion based in-situ Gel for Ocular Delivery of Brimonidine Tartrate

Background: Brimonidine tartrate is currently used to treat glaucoma; however, conventional ocular formulations have some disadvantages in terms of treating disorders like glaucoma, as less than 5% of the drug reaches a posterior segment of the eye; hence, there is a need for sustained treatment. Objective: The objective of this study was to develop a self-nanoemulsion (SNEDDS) in-situ gel of brimonidine tartrate to investigate the sustained-release effect to improve ocular bioavailability. Method: Oil, surfactant, and co-surfactant were screened using the pseudo-ternary phase diagram (TPD) by aqueous-titration method based on the drug solubility. Nanoemulsions were evaluated for the pH, viscosity, % drug content, % transmittance, dispersibility, particle size, zeta-potential, TEM, and conductivity test. Nanoemulsion was incorporated into in-situ gel and evaluated for gelling capacity, pourability, gel strength, in vitro drug release study, and drug release kinetics. Result: Castor oil (10%) as oil phase, Acrysol K-140 (10%) as surfactant, and PEG 400 (20%) as cosurfactant were selected in preparation of SNEDDS from TPD. Evaluation parameters of SNEDDS were found in an acceptable range. % Drug release showed the controlled release up to 8 hrs. Optimum % drug content and % CDR were 100.25% and 92.46% after 12hrs, respectively. Optimized SNEDDS in-situ gel followed the Higuchi model via diffusion mechanism having 0.99 R² value and exhibiting sustained release up to 12 hr. Stability study proved no significant changes during storage. In vitro, the ocular irritancy test proved suitable for ocular delivery. Conclusion: A sustained-release formulation was obtained by developing brimonidine tartrate SNEDDS in-situ gel as a stable formulation without irritancy during ocular administration.

New Improved cGMP Analogues to Target Rod Photoreceptor Degeneration.

Retinitis pigmentosa (RP) is a form of retinal degeneration affecting a young population with an unmet medical need. Photoreceptor degeneration has been associated with increased guanosine 3',5'-cyclic monophosphate (cGMP), which reaches toxic levels for photoreceptors. Therefore, inhibitory cGMP analogues attract interest for RP treatments. Here we present the synthesis of dithio-CN03, a phosphorodithioate analogue of cGMP, prepared using the H-phosphonothioate route. Two crystal modifications were identified as a trihydrate and a tetrahydrofuran monosolvates. Dithio-CN03 featured a lower aqueous solubility than its RP-phosphorothioate counterpart CN03, a drug candidate, and this characteristic might be favorable for sustained-release formulations aimed at retinal delivery. Dithio-CN03 was tested in vitro for its neuroprotective effects in photoreceptor models of RP. The comparison of dithio-CN03 to CN03 and its diastereomer SP-CN03, and to their phosphate derivative oxo-CN03 identifies dithio-CN03 as the compound with the highest efficacy in neuroprotection and thus as a promising new candidate for the treatment of RP.

Formulation Strategies for Sustained-Release Tablet Dosage Forms

Sustained-release or extended-release tablet formulations are designed to release the active pharmaceutical ingredient at a slower rate and over an extended period compared to conventional immediate-release dosage forms. This controlled drug delivery approach offers several advantages including improved patient compliance, maintenance of therapeutic drug levels, reduced side effects, and protection of drug molecules from degradation. [1,2] Various formulation approaches have been explored for achieving sustained drug release from tablet matrices. This review discusses key formulation aspects like rate-controlling polymers, factors influencing drug release, manufacturing techniques, and recent advances aided by quality-by-design principles and mathematical modeling for optimizing sustained-release profiles. Regulatory considerations for evaluation and approval are also highlighted

β-cyclodextrin inclusion complexes with short-chain phenolipids: An effective formulation for the dual sustained-release of phenolic compounds

The β-cyclodextrin and short-chain alkyl gallates (A-GAs), which are representative of phenolipids, such as butyl, propyl, ethyl, and methyl gallates, were chosen to form inclusion complexes by the use of the freeze-drying process. In the everted rat gut sac model, HPLC-UV analysis demonstrated that the released A-GAs from inclusion complexes were degraded to yield free gallic acid (GA) (sustained-release function 1). The small intestine membrane may be crossed by both the GA and the A-GAs. A-GAs may also undergo hydrolysis to provide GA (sustained-release function 2) following transmembrane transfer. Clearly, a helpful technique for the dual sustained-release of phenolic compounds is to produce β-cyclodextrin inclusion complexes with short-chain phenolipids. This will increase the bioactivities of phenolic compounds and prolong their in vivo residence length. Moreover, changing the carbon-chain length of these β-cyclodextrin inclusion complexes would readily modify the dual sustained-release behavior of the phenolic compounds. Thus, our work effectively established a theoretical foundation for the use of β-cyclodextrin inclusion complexes containing short-chain phenolipids as new source of functional food components to provide the body with phenolic compounds more efficiently.

Attenuating mitochondrial dysfunction and morphological disruption with PT320 delays dopamine degeneration in MitoPark mice

BackgroundMitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood.MethodsIn this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse.ResultsOur findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae.ConclusionOur findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD.Graphical

Sustained Release Formulation of Hydroxypropyl-β-cyclodextrin Eye Drops Using Xanthan Gum.

Bietti's crystalline dystrophy (BCD) is an autosomal recessive chorioretinal degeneration caused by mutations in the CYP4V2 gene. It is characterized by cholesterol accumulation and crystal-like deposits in the retinas. Hydroxypropyl-β-cyclodextrin (HP-β-CyD) exerts therapeutic effects against BCD by reducing lysosomal dysfunction and inhibiting cytotoxicity in induced pluripotent stem cell (iPSC)-RPE cells established from patient-derived iPS cells. However, the ocular retention of HP-β-CyD is low and needs to be improved. Therefore, this study used a viscous agent to develop a sustained-release ophthalmic formulation containing HP-β-CyD. Our results suggest that HP-β-CyD-containing xanthan gum has a considerably higher sustained release capacity than other viscous agents, such as methylcellulose and sodium alginate. In addition, the HP-β-CyD-containing xanthan gum exhibited pseudoplastic behavior. It was less cytotoxic to human retinal pigment epithelial cells compared with HP-β-CyD alone. Furthermore, the slow release of HP-β-CyD from xanthan gum caused a sustained decrease in free intracellular cholesterol. These results suggest that xanthan gum is a useful substrate for the sustained release formulation of HP-β-CyD, and that HP-β-CyD-containing xanthan gum has potential as an eye drop for BCD treatment.

Preparation and characterization of injectable in-situ forming gel based on lipid liquid crystal for one month delivery of aripiprazole: In-vitro and in-vivo evaluations in rats

The present study developed a one-month sustained-release formulation of aripiprazole, used for the treatment of schizophrenia and bipolar disorder, based on lipid liquid crystal (LLC) using phosphatidylcholine (PC) and N-methyl-2-pyrrolidone (NMP) solvent with sorbitan monooleate (SMO) or derivative glycerol oleate (glycerol monooleate (GMO), glycerol di-oleate (GDO), and glycerol trioleate (GTO)). The best formulation was selected based on the minimum initial burst release and the highest release of aripiprazole during the 30-day period. So, the formulations containing GMO and SMO exhibited the best initial slow release, while the other two formulations showed a burst release within 24 h. Furthermore, the GMO formulation did not release the drug completely during the 30-day study period, and the formulation containing GTO released the drug completely in less than a month. Therefore, the two formulations containing SMO and GDO were selected for further tests. The prepared liquid crystals had a hexagonal structure, indicating the creation of a suitable formulation structure with slow and controlled release. The area under the curve for the LLC-SMO formulation was higher than for other formulations, supporting the sustained release of aripiprazole and improving the long-term bioavailability of the drug. Moreover, this formulation was found to be safe and did not cause any damage to the skin at the injection site or vital organs such as the spleen, kidney, brain, heart, and liver. Hence, it can be considered a suitable option for developing an extended-release LLC formulation of aripiprazole.

Bioequivalence of Related GelShieldⓇ Sustained-Release Formulations of Metformin: A Pooled Pharmacokinetic Analysis

PurposeGlucophageⓇ (Merck Healthcare KGaA, Darmstadt, Germany) is the originator brand of metformin hydrochloride, an oral antidiabetic drug. Metformin is recommended in guidelines as first-line treatment of type 2 diabetes mellitus and increasingly in related insulin-resistant conditions, such as prediabetes and polycystic ovary syndrome. The GelShieldⓇ sustained-release formulation tablet of GlucophageⓇ has been improved from the historic version marketed in 2000. Bioequivalence has been demonstrated stepwise along this evolution; however, a head-to-head evaluation between the initial and the current version is missing. This analysis aims to close this gap and to determine bioequivalence between related originator GelShieldⓇ sustained-release formulations of metformin, GlucophageⓇ (GXR 500 mg), from Europe and the United States. MethodsData from seven randomized crossover bioequivalence studies in 361 healthy participants of Asian and non-Asian ethnicity from Europe, the United States, and Asia were considered. All evaluated a single oral dose of 500 mg of the test and reference formulation in healthy male and female participants in fed and fasted state. Bioequivalence was evaluated by means of a combined bridging analysis of available data on the current round tablet from Europe (rGXR EU) and the historic oblong tablet from the United States (oGXR US) in healthy Asian and non-Asian participants under fed and fasting conditions. Bioequivalence between the two formulations was assessed statistically with a mixed effects model for AUC0-t, Cmax, and AUC0-inf. FindingsIn all studies, bioequivalence between the respective test and reference formulations of GXR was shown. Statistical analysis of pooled pharmacokinetic data of 2 (primary pooling set) or 3 studies (secondary pooling set) demonstrated bioequivalence between rGXR EU and oGXR US via bridging with oGXR EU. The 90% CI for the geometric mean ratio of all pharmacokinetic parameters was within the bioequivalence range of 0.80 to 1.25. In the primary pooling set, geometric least squares mean ratios in the fed group ranged from 0.9931 (90% CI, 0.9151–1.0778) for AUC0-inf to 1.1344 (90% CI, 1.0711–1.2014) for Cmax; results in the fasted group were similar. The secondary pooling set, which added a study in Asians, confirmed these findings. ImplicationsBioequivalence was determined between sustained-release formulations of GlucophageⓇ from Europe and the United States under fasted and fed conditions in healthy men and women, including different ethnicities. The efficacy and safety of GlucophageⓇ XR can be claimed along the evolution from oGXR US, via oGXR EU to rGXR EU, and in several ethnicities and production sites.

Formulation and Evaluation of Natural Excipient-based Mucoadhesive Salbutamol Sulphate Tablets

When creating a mucoadhesive sustained-release formulation for oral consumption, aquaphilic matrices are a captivating option to consider. These aquaphilic matrices are used to release water-soluble and water-insoluble drugs. Gums and mucilages used in the current study are linseed mucilage (LM) and tamarind seed polysaccharide (TSP). The present work aims to focus on the possibilities of using these polysaccharides to prepare a new medication delivery system. The aim of the research was to make a salbutamol sulfate mucoadhesive tablet for the treatment of asthma. The wet granulation method was adopted for the formulation of the salbutamol sulfate mucosal adhesive tablet. Mucosal adhesive tablets were assessed for multiple parameters. The drug release is low as the amount of gums and mucilages is high. A mucoadhesive tablet containing linseed mucilage and chitosan exhibits good mucoadhesive performance and in-vitro drug release. Optimized formulation FM1 fits the Higuchi plot of release kinetics

Clinical outcomes associated with orphenadrine deliberate self-poisoning: a retrospective poisons centre study

Introduction Orphenadrine overdoses can cause antimuscarinic toxicity, respiratory failure, refractory seizures and cardiotoxicity. The dose–toxicity relationship is poorly defined. Orphenadrine is marketed as immediate and sustained release formulations, and it is not known how the formulation impacts on toxicity. We determined the clinical toxicity of orphenadrine in patients referred to a regional poisons centre. Methods Retrospective case series of patients in New South Wales with orphenadrine deliberate self-poisoning from January 2016 to April 2022 referred to the New South Wales Poisons Information Centre. Demographics, history of exposure, treatment and outcomes were extracted from clinical databases. Receiver-operating characteristic curves were constructed to determine thresholds predicting toxicity. Results Forty-eight patients were identified, with information on clinical outcomes in 46 patients and doses in 41 patients. All patients were older than 12 years. The median orphenadrine dose was 770 mg (range 210–10,000 mg), 59 per cent as the immediate release formulation, and 67 per cent reported coingestants. Doses of sustained release formulations were significantly greater than immediate release formulations, median 2,750 mg versus 595 mg. Common clinical features were drowsiness (59 per cent), sinus tachycardia (37 per cent) and confusion (33 per cent). Three patients had mild hypotension, three were intubated for coma, and two had seizures; no patients suffered ventricular dysrhythmias. All patients survived, with 75 per cent being medically cleared within 24 hours of presentation. A dose–toxicity relationship was observed, but conclusions are limited by the small number of cases with moderate or severe toxicity. Discussion All patients survived, and severe cardiac and neurological toxicity were not observed. This contrasts to published case reports noting severe poisoning at similar or lower doses. Formulation may have an impact on outcomes, with lesser toxicity from sustained release products. Conclusions Orphenadrine doses up to 10 g were associated with antimuscarinic toxicity and sedation, but not severe cardiotoxicity. More research exploring the effect of dose and formulation on outcomes is required.

Quality by Design and Characterization of Nimodipine Novel Carriers for the Treatment of Hypertension: Assessment of the Pharmacokinetic Profile

Background: Nimodipine is a highly lipophilic anti-hypertensive drug having 13% oral bioavailability (log P 3.41). Nimodipine is a prominent calcium channel blocker that must be given intravenously for an extended period of time (1-2 weeks) in order to treat cerebral vasospasm. It might be possible to substitute a sustained-release biodegradable formulation for the ongoing intravenous infusion used in this traditional therapy. Objectives: The primary goal of this study was to formulate and evaluate the potentiality of ethosomes to deliver nimodipine, a potent water-insoluble anti-hypertensive drug, through the deeper layers of the skin. The greatest challenge for drug formulation is its poor oral bioavailability and solubility. Methods: Nimodipine-loaded ethosomal gel was developed for transdermal drug delivery to increase solubility and skin penetration and to promote oral bioavailability. Central composite design employing a thin-film hydration method was used to prepare and optimize ethosomes. A better dispersion medium for nimodipine's preparation in ethosomes was selected based on the effect. The design consisted of independent variables as lipid (X1), ethanol (X2), and sonication time (X3). Concentrations were manipulated to examine the effects on three responses, namely the %entrapment efficiency (Y1), vesicle size (Y2), and %cumulative drug release (Y3). Surface morphology and other in vitro tests were used to identify ethosomes containing nimodipine. The preparation of ethosomal gel formulations began with incorporating a single ethosomal formulation (F4) into various concentrations of gelling agents. These studies performed physicochemical characterization, compatibility testing, and in vitro drug release tests on ethosomal gels. In vivo studies involving hypertensive rats were conducted after skin permeation, and ex vivo studies were performed. In order to assess the drug's permeability and deposition, we employed the abdomen skin of rats. Results: The optimal process parameters resulted in ethosomes with 89.9 ± 0.19 percent entrapment efficiency, a vesicle size of 102.37 ± 5.84 nm, and a cumulative drug release of 98.3 ± 0.13%. pH and drug content measurements were consistent with the homogeneous ethosomal gels. Viscosity was found to increase with the spreadability. The ethosomal gel formulation (G2) met the regulatory standards regarding appearance, spreadability, viscosity, and in vitro release studies. Compared to pure nimodipine, ethosomal suspension (F4) and ethosomal gel (G2) formulations had higher ex vivo permeation, steady-state flux, and drug retention. Rats' mean arterial pressure (146.11 ± 0.84 mmHg) was significantly lower (p < 0.01) after after two hours of the experiment than it had been (p < 0.001) (98.88 ± 0.63 mmHg) after six hours. Conclusion: To summarize, ethosomal gels have been found to be lipid carriers that enhance skin permeation and extend the anti-hypertensive effect of nimodipine. Compared to plain gel, ex vivo drug permeation through rat abdominal skin in ethosomal gel was enhanced. Gel-based ethosomal transdermal drug delivery formulations of nimodipine can be used to achieve a faster rate and extend the duration of drug delivery by more than 24 hours.

Electrospinning synthesis of nanofiber membrane with biodegradable as sustained-release formulation of fenofibrate

Fenofibrate is widely used as a lipid-lowering drug. However, fenofibrate has a short half-life, so it needs to be prepared as a sustained-release preparation to prolong the administration time. In this study, fenofibrate nanofibers are prepared by electrospinning using the biodegradable material polylactic acid as a drug carrier. To improve the hydrophilicity and cumulative drug release rate, polyvinylpyrrolidone is introduced to prepare a composite drug-loaded nanofibrous membrane. The experimental results show that the hydrophilicity and cumulative release rate are improved. This study provides a simple and efficient method for the preparation of fenofibrate nanofibrous membranes with sustained-release effects.

Formulation and In Vitro Evaluation of Diacerein Microspheres Using Ethyl-cellulose as Rate Retarding Agent

Diacerein is a newly developed anti-inflammatory drug that is chemically and pharmacologically different from NSAIDs. Diacerein is poorly soluble in water and possesses a slower dissolution rate. The development of Diacerein microspheres improved the aqueous solubility and the drug dissolution rate. Similarly, Diacerein microspheres enabled us to control the drug's release rate and minimize the dosing frequency. The solvent evaporation method prepared diacerein microspheres using ethyl cellulose and hydroxyl propyl cellulose as encapsulation material. In this study, six different formulations were prepared using different proportions of ethyl cellulose, and two formulations encompassing different combinations of ethyl cellulose and hydroxyl propyl cellulose were prepared. Different proportions of gelatin were used as emulsifying agents. The formulated microspheres were evaluated through FTIR, SEM, %age yield, chemical assay, release kinetics, in vitro dissolution studies, and entrapment efficiency. FTIR spectra depicted that there was no drug-to-polymer interaction. SEM confirmed the spherical nature of microspheres, and the drug entrapment efficiency was 89%. Our study demonstrates that microspheres could be a suitable technique to formulate DCN sustained release formulation.

Design and Characterization of Oral Mucoadhesive Buccal Films of Empagliflozin

An anti-diabetic drug called Empagliflozin is used to control blood glucose levels in type 2 diabetics. Due to the high rate of hepatic first pass metabolism, it exhibits limited bioavailability. The current study was done to create Mucoadhesive buccal films of Empagliflozin with the aim of increasing bioavailability, patient compliance, and therapeutic efficacy. The solvent casting process used for the preparation of Empagliflozin Mucoadhesive buccal films by using the Mucoadhesive polymers like HPMC K100 and HEC. The prepared films' evaluated for weight variation, thickness, surface pH, uniformity of the drug content, in-vitro residence time, folding durability, in-vitro release, and permeation investigations were all assessed. Formulations (F1-F4) were created by altering the concentrations of various polymers, with F2 and F4 formulations having the highest polymer ratios and the longest-lasting drug release rates. According to characterization results such as in-vitro dissolution experiments, the sustained release formulation F2, F4 shows the best drug release rate, the order of drug release is F1>F3>F2>F4. It was determined that the films could be chosen for the development of buccal films for effective therapeutic applications because they exhibited effective enlargement, a practicable residence duration, and promising controlled drug release.

The Application of Response Surface Methodology (RSM) In the Computational Optimization of Sustained Release (SR) For Phenothiazine Derivative Matrix Tablet

Introduction: This study explores the use of Response Surface Methodology (RSM), a statistical optimization technique, to optimize the SR properties of prochlorperazine maleate (PCM) matrix tablets. PCM is a phenothiazine derivative used for treating schizophrenia, nausea, and vomiting. Sustained-release formulations offer extended drug delivery, potentially improving patient compliance and reducing side effects. RSM helps identify optimal combinations of critical formulation factors influencing drug release, such as polymer type and concentration, filler type, and drug/polymer ratio. The study likely involves designing experiments based on chosen RSM designs (e.g., Box-Behnken) with varying factor levels. Formulate SR tablets with different factor combinations. Evaluating the drug release profiles of each tablet formulation. Analyzing data using RSM software to build mathematical models relating factors to drug release and identifying optimal factor combinations that maximize desired release characteristics. Objective: The ongoing research purpose to improve the advancement of a sustained release tablet containing Phenothiazine derivative PCM loaded matrix. This is achieved by utilizing DoE as a computational method to statistically validate the formulation. Methodology: Basically two methods involved in the formulation using direct compression; a simple and efficient method where all dry ingredients are blended and directly compressed into tablets. Results: The obtained outcomes closely matched the anticipated values derived from the experimental setup. The enhanced PCM matrix tablets demonstrated a prolonged and uniform discharge of PCM over a span of 6 hours. Conclusion: This study Based on a 23 FD, response surface methodology was used to successfully develop the current research of PCM matrix tablets for sustained release application. The corresponding contour plots and 3D response methodology represent the important variables for the optimisation process.

Leptospermum honey – A medicinal wonder for periodontal health

Antibacterial therapy has always been included effectively in the regimen of periodontitis. The inability to access periodontal disease-causing organisms within periodontal pockets has limited the effectiveness of mechanical plaque removal and the use of antibacterial agents. The drug’s systemic administration results in therapeutic concentrations at the site of infection, but only in the short term, necessitating repeated dosing over longer periods. Topical antibiotics have been studied for their ability to overcome the limitations of conventional therapy. It is of interest to use sustained release formulations to deliver antimicrobial agents to the site of infection (periodontal pocket). At much lower doses, these products provide long-term treatment at the site of infection. From time immemorial, honey is not only considered as a natural sweetener but is also used for its healing power. It is used in traditional folk and tribal medicines and 93% of the consumers of honey use it for its medicinal value. Active Leptospermum Honey (ALH) is the most researched medical grade honey for wound and burn treatment. This article documents the efficacy of ALH as a topical drug delivery system in patients with chronic periodontal disease.

Effect of hot-melt extruded Morus alba leaves on intestinal microflora and epithelial cells

Although rutin and isoquercitrin have many effects, they are insoluble substances, making it difficult to obtain pure substances. This study was to investigate whether Morus alba leaves containing rutin and isoquercitrin could improve intestinal health by making a sustained-release formulation through a hot-melt extrusion (HME) process with improved stability and solubility and determine whether it could upregulate the balance of intestinal microorganisms and intestinal epithelial cells. A sustained-release formulation was prepared by the HME process using Morus alba leaves and a hydrophilic polymer matrix. Antibacterial activities of pathogenic microorganisms (Escherichia coli, Streptococcus aureus, Enterococcus faecalis) and proliferative effect of probiotics (Lactobacillus rhamnosus, Pediococcus pentosaceus) were tested against intestinal microorganisms. Regarding intestinal epithelial cells, a co-culture model of Caco-2 cells and RAW 264.7 cells was used. It was confirmed that the extrudate exhibited high antibacterial activities against pathogenic microorganisms and affected the proliferation of probiotics. Furthermore, after inducing inflammation through LPS, it recovered transepithelial electrical resistance-increased levels of tight junction proteins and decreased expression levels of pro-inflammatory cytokines. HME of Morus alba leaves containing rutin and isoquercitrin can upregulate intestinal microbial balance and intestinal epithelial cells.

Development, Physicochemical Characteristics and Pharmacokinetics of a New Sustained-Release Bilayer Tablet Formulation of Tramadol with an Immediate-Release Component for Twice-Daily Administration.

There are some potential concerns about the currently marketed solid oral dosage forms of tramadol, including decreased adherence to immediate-release (IR) formulations due to the high number of doses taken each day and the slow rise in the blood tramadol concentration after administration of sustained-release (SR) formulations, which may not achieve a rapid analgesic effect. To overcome these potential concerns, a twice-daily double-layered tablet formulation of tramadol comprising IR and SR layers was developed. This article reports studies that assessed its physicochemical and pharmacokinetic properties. Dissolution tests of five bilayer tablet formulations (designated tablets A-E) and pharmacokinetic studies of tablets A and B were conducted to investigate the appropriate ratio of the IR/SR layers in the double-layered tablet. Additionally, pharmacokinetic studies of three finished dosage formulations (tablets C-E) were performed in healthy adult males to investigate the effect of food intake on drug absorption. Adjusting the excipients and tramadol content in the IR and SR layers of tablets A-E altered their dissolution profiles in a manner that could be predicted based on their compositions. The IR layer was released within 15min, and the SR layer was slowly released over 10h. In the pharmacokinetic study, the time to maximum plasma concentration (tmax) of tramadol after administration of tablets A (IR:SR: 20:80mg) and B (40:60mg) was shorter than that of a commercially available SR tablet, and the half-life (t1/2) was longer than that of a commercially available IR tablet. For tablets C-E, administration after food did not affect the area under theconcentration-time curve (AUC) or maximum drug concentration (Cmax) of tramadol, but the tmax was prolonged by about 1 h compared with administration in fasting conditions. The mean ± standard deviation tmax and t1/2 for tablet D (IR:SR: 35:65 mg) in the fasting condition was 1.09 ± 0.56h and 7.82 ± 0.85h, respectively. The respective values in the fed condition were 2.47 ± 1.06h and 7.12 ± 0.85h, respectively. To address the potential concerns regarding existing formulations of tramadol, a twice-daily, extended-release bilayer formulation of tramadol consisting of an IR and SR layer was developed. Pharmacokinetic studies confirmed that the plasma tramadol concentration increased quickly after administration and was maintained over a long period of time.

Biomaterial-Based Sustained-Release Drug Formulations for Localized Cancer Immunotherapy.

Cancer immunotherapy has revolutionized clinical cancer treatments by taking advantage of the immune system to selectively and effectively target and kill cancer cells. However, clinical cancer immunotherapy treatments often have limited efficacy and/or present severe adverse effects associated primarily with their systemic administration. Localized immunotherapy has emerged to overcome these limitations by directly targeting accessible tumors via local administration, reducing potential systemic drug distribution that hampers drug efficacy and safety. Sustained-release formulations can prolong drug activity at target sites, which maximizes the benefits of localized immunotherapy to increase the therapeutic window using smaller dosages than those used for systemic injection, avoiding complications of frequent dosing. The performance of sustained-release formulations for localized cancer immunotherapy has been validated preclinically using various implantable and injectable scaffold platforms. This review introduces the sustained-release formulations developed for localized cancer immunotherapy and highlights their biomaterial-based platforms for representative classes, including inorganic scaffolds, natural hydrogels, synthetic hydrogels, and microneedle patches. The design rationale and other considerations are summarized for further development of biomaterials for the construction of optimal sustained-release formulations.