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AbstractBackgroundMethodsResultsConclusions\nSHORT CONDENSATIONDienogest (DNG) 2 mg/ethinylestradiol (EE) 0.02 mg is the first low-dose combined oral contraceptive (COC) with a prolonged-release formulation that allows stable plasma concentrations and has high contraceptive efficacy (Pearl index: 0.2). The aim of this trial was to determine the bleeding profile of this contraceptive compared to an immediate release formulation.This prospective double-blind randomised controlled trial evaluated the bleeding patterns of DNG 2 mg/EE 0.02 mg compared with immediate-release drospirenone (DRSP) 3 mg/EE 0.02 mg in a 24/4-day regimen over nine cycles (randomisation ratio, 5:2). Participants recorded scheduled and unscheduled bleeding/spotting data using an electronic diary. A non-inferiority analysis for the proportion of participants with unscheduled bleeding/spotting was prespecified for Cycles 2–6. Safety, including adverse events, were monitored throughout the trial.Seven-hundred six and 288 participants received DNG/EE and DRSP/EE, respectively. Scheduled bleeding patterns per each 28-day cycle were similar in both groups. During Cycles 2–6, the proportion of participants with unscheduled bleeding/spotting was significantly lower in the DNG/EE group (50.5% [280/574] than in the DRSP/EE group (72.8% [171/235]]; treatment difference 22.3% [95% CI 15.9, 28.6%]; p < 0.0001). A low proportion of participants discontinued the trial due to bleeding disorders (1.7% and 0.7%, respectively). The safety profiles were similar for both treatments.The prolonged-release DNG 2 mg/EE 0.02 mg offers a significant decrease in unscheduled bleeding/spotting compared with an immediate-release COC, DRSP/EE, combined with high contraceptive efficacy and a very low adverse event profile.The prolonged-release DNG 2 mg/EE 0.02 mg offers a significant decrease in unscheduled bleeding compared with an immediate-release COC while maintaining contraceptive efficacy and with no new safety signals. [ABSTRACT FROM AUTHOR]

Minitablets have been extensively studied in recent years as a convenient pediatric form because they allow successful administration even in very young children. Their advantages include easy dose adjustment by multiplication of single units as well as the possibility of drug release modification by coating or forming matrix systems. The aim of this study was to demonstrate the possibility of the formulation of prolonged-release minitablets with bromhexine hydrochloride (BHX) and bisoprolol fumarate (BFM) dedicated to pediatric patients. Minitablets with 3 mm diameter and 15 mg mass, containing 1 mg of active substance in 1 unit, were prepared by direct compression with hydroxypropyl methylcellulose (HPMC) of different grades, methylcellulose, sodium alginate, or polyvinyl alcohol (PVA) as a sustained-release polymer. Different amounts of polymers and different compression forces were evaluated. Analysis of minitablets included their uniformity, hardness, and dissolution tests. The kinetics of drug substance release were analyzed with dedicated software. The prepared minitablets met the pharmacopeial requirements with respect to the uniformity of mass and content. The compressibility of BFM was significantly better than that of BHX, yet all minitablets had good mechanical properties. Dissolution studies showed a strong relationship between the type of polymer and its amount in the mass of a tablet and the dissolution rate. Prolonged release of up to 8 h was achieved when HPMC of 4000 cP viscosity was used in the amount of 30% to 80%. Sodium alginate in the amount of 50% was also effective in prolonging dissolution, but PVA was much less effective. Studies on the release kinetics showed that dissolution from prolonged-release minitablets with BHX fit the best to Hopfenberg or Hixson–Crowell models, while in the case of BFM, the best fit was found for Hopfenberg or Korsmeyer–Peppas models. [ABSTRACT FROM AUTHOR]

The mathematical models available in DDSolver were applied to experimental dissolution data obtained by analysing carvedilol release from hypromellose (HPMC)-based matrix tablets. Different carvedilol release profiles were generated by varying a comprehensive selection of fillers and carvedilol release modifiers in the formulation. Model fitting was conducted for the entire relevant dissolution data, as determined by using a paired t-test, and independently for dissolution data up to approximately 60% of carvedilol released. The best models were selected based on the residual sum of squares (RSS) results used as a general measure of goodness of fit, along with the utilization of various criteria for visual assessment of model fit and determination of the acceptability of estimated model parameters indicating burst release or lag time concerning experimental dissolution results and previous research. In addition, a model-dependent analysis of carvedilol release mechanisms was carried out. [ABSTRACT FROM AUTHOR]

This multifaceted landscape of long-acting gels in diverse medical fields, aims to enhance therapeutic outcomes through localized treatment and controlled drug release. The objective involves advancements spanning cancer treatment, immunotherapy, diabetes management, neuroendocrine disorders, ophthalmic applications, contraception, HIV/AIDS treatment, chronic diseases, wound care, and antimicrobial treatments. It explores the potential of long-acting gels to offer sustained and extended drug release, targeted therapy, and innovative administration routes while addressing limitations such as scalability challenges and regulatory hurdles. Future directions focus on personalized therapies, biodegradability, combination therapies, interdisciplinary innovation, regulatory considerations, and patient-centric development. This comprehensive review highlights the pivotal role of long-acting gels in transforming therapeutic approaches and improving patient outcomes across various medical conditions. [ABSTRACT FROM AUTHOR]

Allapinin has antiarrhythmic activity and can be used to prevent and treat various supraventricular and ventricular arrhythmias. Nevertheless, it is highly toxic and has a number of side effects associated with non-specific accumulation in various tissues. The complex of this substance with the monoammonium salt of glycyrrhizic acid (Al:MASGA) has less toxicity and improved antiarrhythmic activity. However, the encapsulation of Al:MASGA in polyelectrolyte microcapsules (PMC) for prolonged release will reduce the residual adverse effects of this drug. In this work, the possibility of encapsulating the allapinin–MASGA complex in polyelectrolyte microcapsules based on polyallylamine and polystyrene sulfonate was investigated. The encapsulation methods of the allapinin–MASGA in polyelectrolyte microcapsules by adsorption and coprecipitation were compared. It was found that the coprecipitation method did not result in the encapsulation of Al:MASGA. The sorption method facilitated the encapsulation of up to 80% of the original substance content in solution in PMC. The release of the encapsulated substance was further investigated, and it was shown that the release of the encapsulated Al:MASGA was independent of the substance content in the capsules, but at pH 5, a two-fold decrease in the rate of drug release was observed. [ABSTRACT FROM AUTHOR]

Background: Meltdose tacrolimus (Envarsus®) has been marketed as a formulation achieving a more consistent tacrolimus exposure. Due to the narrow therapeutic window of tacrolimus, dose individualization is essential. Relaxation of the upper age limits for kidney transplantations has resulted in larger numbers of elderly patients receiving tacrolimus. However, due to the physiological changes caused by aging, the tacrolimus pharmacokinetics (PK) might be altered. The primary aim was to develop a population PK model in elderly kidney transplant recipients. Secondary aims were the development and evaluation of a limited sampling strategy (LSS) for AUC estimation. Methods: A total of 34 kidney transplant recipients aged ≥65 years, starting on meltdose tacrolimus directly after transplantation, were included. An eight-point whole blood AUC0–24h and an abbreviated dried blood spot (DBS) AUC0–24h were obtained. The PK data were analyzed using nonlinear mixed effect modeling methods. Results: The PK data were best described using a two-compartment model, including three transit compartments and a mixture model for oral absorption. The best three-sample LSS was T = 0, 2, 6 h. The best four-sample LSSs were T = 0, 2, 6, 8 h and T = 0, 1, 6, 8 h. Conclusions: The developed population PK model adequately described the tacrolimus PK data in a population of elderly kidney transplant recipients. In addition, the developed population PK model and LSS showed an adequate estimation of tacrolimus exposure, and may therefore be used to aid in tacrolimus dose individualization. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that results in the deterioration of joint cartilage and bone. Toll-like receptor 4 (TLR4) has been pinpointed as a key factor in RA-related inflammation. While Toll-like receptor antagonizing peptide 2 (TAP2) holds potential as an anti-inflammatory agent, its in vivo degradation rate hinders its efficacy. We engineered depots of TAP2 encapsulated in click-crosslinked hyaluronic acid (TAP2+Cx-HA) for intra-articular administration, aiming to enhance the effectiveness of TAP2 as an anti-inflammatory agent within the joint cavity. Our data demonstrated that FI-TAP2+Cx-HA achieves a longer retention time in the joint cavity compared to FI-TAP2 alone. Mechanistically, we found that TAP2 interacts with TLR4 on the cell membranes of inflammatory cells, thereby inhibiting the nuclear translocation of NF-κB and maintaining it in an inactive cytoplasmic state. In a rat model of RA, the TAP2+Cx-HA formulation effectively downregulated the inflammatory cytokines TNF-α and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3ζ. This led to a more rapid restoration of cartilage thickness, increased deposition of glycosaminoglycans, and new bone tissue formation in the regenerated cartilage, in comparison to a single TAP2 treatment after a six-week period. Our results suggest that TAP2+Cx-HA could serve as a potent intra-articular treatment for RA, offering both symptomatic relief and promoting cartilage regeneration. This innovative delivery system holds significant promise for improving the management of RA and other inflammatory joint conditions. In this study, we developed a therapy by creating toll-like receptor 4 (TLR4)-antagonizing peptide (TAP2)-loaded click-crosslinked hyaluronic acid (TAP2+Cx-HA) depots for direct intra-articular injection. Our study demonstrates that FI-TAP2+Cx-HA exhibits a more than threefold longer lifetime in the joint cavity compared to FI-TAP2 alone. Furthermore, we found that TAP2 binds to TLR4 and masks the nuclear localization signals of NF-κB, leading to its sequestration in an inactive state in the cytoplasm. In a rat model of RA, TAP2+Cx-HA effectively suppresses inflammatory molecules, specifically TNF–α and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3ζ. This resulted in faster regeneration of cartilage thickness, increased glycosaminoglycan deposits in the regenerated cartilage, and a twofold increase in new bone tissue formation compared to a single TAP2 treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Minitablets have been extensively studied in recent years as a convenient pediatric form because they allow successful administration even in very young children. Their advantages include easy dose adjustment by multiplication of single units as well as the possibility of drug release modification by coating or forming matrix systems. The aim of this study was to demonstrate the possibility of the formulation of prolonged-release minitablets with bromhexine hydrochloride (BHX) and bisoprolol fumarate (BFM) dedicated to pediatric patients. Minitablets with 3 mm diameter and 15 mg mass, containing 1 mg of active substance in 1 unit, were prepared by direct compression with hydroxypropyl methylcellulose (HPMC) of different grades, methylcellulose, sodium alginate, or polyvinyl alcohol (PVA) as a sustained-release polymer. Different amounts of polymers and different compression forces were evaluated. Analysis of minitablets included their uniformity, hardness, and dissolution tests. The kinetics of drug substance release were analyzed with dedicated software. The prepared minitablets met the pharmacopeial requirements with respect to the uniformity of mass and content. The compressibility of BFM was significantly better than that of BHX, yet all minitablets had good mechanical properties. Dissolution studies showed a strong relationship between the type of polymer and its amount in the mass of a tablet and the dissolution rate. Prolonged release of up to 8 h was achieved when HPMC of 4000 cP viscosity was used in the amount of 30% to 80%. Sodium alginate in the amount of 50% was also effective in prolonging dissolution, but PVA was much less effective. Studies on the release kinetics showed that dissolution from prolonged-release minitablets with BHX fit the best to Hopfenberg or Hixson–Crowell models, while in the case of BFM, the best fit was found for Hopfenberg or Korsmeyer–Peppas models.

The prolonged release tablets form of alimemazine is seen as a promising agent for the long-term treatment of generalized anxiety disorder (GAD).Objective: to investigate the efficacy and safety of therapy with alimemazine (Teraligen® retard, prolonged release film-coated tablets) in patients with GAD.Material and methods. The study design was a multicentre, open-label, non-comparative clinical trial (CT) with two doses of alimemazine 20 and 40 mg (Teraligen® retard, prolonged-release film-coated tablets). 129 patients diagnosed with GAD (criteria according to the ICD-10 classification), 86 women and 43 men were included, mean age 38.0±11.1 years. The level of anxiety, assessed by the Hamilton HARS scale, at Week 0 (Visit 1) was 24.8±7.3 points.Results. By Week 6, the level of anxiety statistically significantly decreased to a mean score of 10.8±6.6, while the dynamics of the mean score relative to baseline was -14.0±6.27 (p

The development of new film-forming compositions based on polyurethane ureas and dacarbazine will make it possible to obtain new polymer systems for local prolonged release of an anticancer drug as adjuncts to anticancer therapy. To solve the problem composite materials with 1 wt. % dacarbazine (DK) on the basis of polyurethane ureas (PUU) containing in the structure as macrochain extenders of 2-(2-aminoethoxy)ethan-1-amine, (DA1) 3,6-dioxaoctane-1,8-diamine (DA2) 3-{2-[2-(3-aminopropoxy)ethoxy]ethoxy}propan-1-amine (DA3) with a molar ratio of 4,4'-diaminodiphenylmethane (DADPh) to DA1, DA2 and DA3 as 0,7:0,3; 0,3:0,7; 0,7:0,3 were obtained The tensile strength of the compositions is within (1.21-1.27) MPa, the relative elongation is (303.9-384,2)%. Studies of thermophysical properties of synthesized PUU by DSC, TGA methods were conducted. Dacarbazine compositions are single-phase systems with glass transition temperature (Tg) from -33.55 °C to -37.06 °C. It was established that the introduction of Dacarbazine into the composition of PUU leads to a decrease in Tg and ΔCp during the second warm-up in comparison with the original PUU. Dacarbazine compositions are resistant to temperatures of 270 °C, which allows for thermal sterilization before use. The release of Dacarbazine from polymer samples into the solution was studied by the spectrophotometric method. According to the results of the study of the dynamics release of Dacarbazine, it was es tablished that for (PUU DA1)2+DK in 14 days it is 61.74 %, (PUU DA2)4+DK - 70.09 %, (PUU DA3)2+DK - 56.75 % of the total amount of immobilized DK. The resulting composites are perspective materials for medicine as means of local prolonged therapeutic action. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) and its complications are one of the leading causes of death worldwide, with approximately 700 million people expected to suffer from DM by 2045, according to the International Diabetes Federation. DM is a progressive, chronic disease that affects various body systems and can lead to serious physical health complications. Type 2 diabetes mellitus (T2DM) has been shown to be associated with a higher incidence of sleep disturbances, which may be due to the disease itself or secondary complications or comorbidities associated with DM. However, epidemiological evidence suggests a higher risk of obesity, metabolic syndrome, and T2DM in individuals with shorter sleep duration and poor quality of sleep. Therefore, an assessment of the quality of sleep, its disorders and their pharmacological correction is recommended as a comprehensive medical examination for existing T2DM and for groups at risk of its development. Among pharmacotherapeutic agents for the treatment of sleep disorders, melatonin (N-acetyl-5-methoxytryptamine) attracts special attention. It is indoleamine, a pineal hormone synthesized in the human body, which name is related to the ability to aggregate melanin pigment granules. It has been found that melatonin directly participates in many biological processes and limits oxidative stress both extracellularly and intracellularly. Endogenous melatonin has linear kinetics, the half-life of the usual form of melatonin with rapid release ranges from 45 to 65 minutes, it is quickly metabolized and is completely excreted after 3–4 hours. Currently, 1 and 2 mg prolonged-release forms of melatonin are available, which provide slower and longer absorption, a delayed and lower peak dose, and levels maintained for 8 to 10 hours — similar to the physiological secretion curve of endogenous melatonin. Since the dose of melatonin in prolonged-release forms is much lower than in immediate release forms, this will help reduce the risk of possible side effects, including in patients with T2DM and in groups at risk of its development.

This multifaceted landscape of long-acting gels in diverse medical fields, aims to enhance therapeutic outcomes through localized treatment and controlled drug release. The objective involves advancements spanning cancer treatment, immunotherapy, diabetes management, neuroendocrine disorders, ophthalmic applications, contraception, HIV/AIDS treatment, chronic diseases, wound care, and antimicrobial treatments. It explores the potential of long-acting gels to offer sustained and extended drug release, targeted therapy, and innovative administration routes while addressing limitations such as scalability challenges and regulatory hurdles. Future directions focus on personalized therapies, biodegradability, combination therapies, interdisciplinary innovation, regulatory considerations, and patient-centric development. This comprehensive review highlights the pivotal role of long-acting gels in transforming therapeutic approaches and improving patient outcomes across various medical conditions.

The mathematical models available in DDSolver were applied to experimental dissolution data obtained by analysing carvedilol release from hypromellose (HPMC)-based matrix tablets. Different carvedilol release profiles were generated by varying a comprehensive selection of fillers and carvedilol release modifiers in the formulation. Model fitting was conducted for the entire relevant dissolution data, as determined by using a paired t-test, and independently for dissolution data up to approximately 60% of carvedilol released. The best models were selected based on the residual sum of squares (RSS) results used as a general measure of goodness of fit, along with the utilization of various criteria for visual assessment of model fit and determination of the acceptability of estimated model parameters indicating burst release or lag time concerning experimental dissolution results and previous research. In addition, a model-dependent analysis of carvedilol release mechanisms was carried out.

Nanocarriers for oxygen delivery have been the focus of extensive research to ameliorate the therapeutic effects of current anti-cancer treatments and in the organ transplant field. In the latter application, the use of oxygenated cardioplegic solution (CS) during cardiac arrest is certainly beneficial, and fully oxygenated crystalloid solutions may be excellent means of myocardial protection, albeit for a limited time. Therefore, to overcome this drawback, oxygenated nanosponges (NSs) that can store and slowly release oxygen over a controlled period have been chosen as nanocarriers to enhance the functionality of cardioplegic solutions. Different components can be used to prepare nanocarrier formulations for saturated oxygen delivery, and these include native α-cyclodextrin (αCD), αcyclodextrin-based nanosponges (αCD-NSs), native cyclic nigerosyl-nigerose (CNN), and cyclic nigerosyl-nigerose-based nanosponges (CNN-NSs). Oxygen release kinetics varied depending on the nanocarrier used, demonstrating higher oxygen release after 24 h for NSs than the native αCD and CNN. CNN-NSs presented the highest oxygen concentration (8.57 mg/L) in the National Institutes of Health (NIH) CS recorded at 37 °C for 12 h. The NSs retained more oxygen at 1.30 g/L than 0.13 g/L. These nanocarriers have considerable versatility and the ability to store oxygen and prolong the amount of time that the heart remains in hypothermic CS. The physicochemical characterization presents a promising oxygen-carrier formulation that can prolong the release of oxygen at low temperatures. This can make the nanocarriers suitable for the storage of hearts during the explant and transport procedure. [ABSTRACT FROM AUTHOR]

This study aimed to develop a prolonged-release system based on palygorskite and chitosan, which are natural ingredients widely available, affordable, and accessible. The chosen model drug was ethambutol (ETB), a tuberculostatic drug with high aqueous solubility and hygroscopicity, which is incompatible with other drugs used in tuberculosis therapy. The composites loaded with ETB were obtained using different proportions of palygorskite and chitosan through the spray drying technique. The main physicochemical properties of the microparticles were determined using XRD, FTIR, thermal analysis, and SEM. Additionally, the release profile and biocompatibility of the microparticles were evaluated. As a result, the chitosan–palygorskite composites loaded with the model drug appeared as spherical microparticles. The drug underwent amorphization within the microparticles, with an encapsulation efficiency greater than 84%. Furthermore, the microparticles exhibited prolonged release, particularly after the addition of palygorskite. They demonstrated biocompatibility in an in vitro model, and their release profile was influenced by the proportion of inputs in the formulation. Therefore, incorporating ETB into this system offers improved stability for the administered product in the initial tuberculosis pharmacotherapy dose, minimizing its contact with other tuberculostatic agents in the treatment, as well as reducing its hygroscopicity. [ABSTRACT FROM AUTHOR]

Julie Rolling1– 4&ast;, Juliette Rabot1– 3,5,6&ast;, Carmen M Schroder1– 6 1Department of Child and Adolescent Psychiatry, Strasbourg University Hospitals, Strasbourg, France; 2CNRS UPR3212- Research Team “Light, Circadian Rhythms, Sleep Homeostasis and Neuropsychiatry”, Institute of Cellular and Integrative Neurosciences, Strasbourg, France; 3Excellence Centre for Autism and Neurodevelopmental Disorders STRAS&ND, Strasbourg, France; 4Sleep Disorders Centre & International Research Centre for ChronoSomnology (Circsom), University Hospitals Strasbourg, Strasbourg, France; 5Expert Centre for High-Functioning Autism, Fondation FondaMental, Strasbourg, France; 6Autism Resources Centre 67 for Children and Adolescents, Strasbourg, France&ast;These authors contributed equally to this workCorrespondence: Carmen M Schroder, Email schroderc@unistra.frAbstract: Sleep is a vital physiological function that is impaired in ranges from 10% in the typically developing pediatric population to over 80% in populations of children with neurodevelopmental disorders and/or psychiatric comorbidities. Pediatric insomnia disorder is an increasing public health concern given its negative impact on synaptic plasticity involved in learning and memory consolidation but also on mood regulation, hormonal development and growth, and its significant impact on quality of life of the child, the adolescent and the family. While first-line treatment of pediatric insomnia should include parental education on sleep as well as sleep hygiene measures and behavioural treatment approaches, pharmacological interventions may be necessary if these strategies fail. Melatonin treatment has been increasingly used off-label in pediatric insomnia, given its benign safety profile. This article aims to identify the possible role of melatonin treatment for pediatric insomnia, considering its physiological role in sleep regulation and the differential effects of immediate release (IR) versus prolonged release (PR) melatonin. For the physician dealing with pediatric insomnia, it is particularly important to be able to distinguish treatment rationales implying different dosages and times of treatment intake. Finally, we discuss the benefit–risk ratio for melatonin treatment in different pediatric populations, ranging from the general pediatric population to children with different types of neurodevelopmental disorders, such as autism spectrum disorder or ADHD.Keywords: melatonin, prolonged release, immediate release, pediatric insomnia, sleep, circadian, autism spectrum disorder, ADHD, delayed sleep phase syndrome

Solid dosage forms based on hypromellose (HPMC) with prolonged/extended drug release are very important from the research and industrial viewpoint. In the present research, the influence of selected excipients on carvedilol release performance from HPMC-based matrix tablets was studied. A comprehensive group of selected excipients was used within the same experimental setup, including different grades of excipients. Compression mixtures were directly compressed using constant compression speed and main compression force. LOESS modelling was used for a detailed comparison of carvedilol release profiles via estimating burst release, lag time, and times at which a certain % of carvedilol was released from the tablets. The overall similarity between obtained carvedilol release profiles was estimated using the bootstrapped similarity factor (f2). In the group of water-soluble carvedilol release modifying excipients, which produced relatively fast carvedilol release profiles, POLYOXᵀᴹ WSR N-80 and Polyglykol® 8000 P demonstrated the best carvedilol release control, and in the group of water-insoluble carvedilol release modifying excipients, which produced relatively slow carvedilol release profiles, AVICEL® PH-102 and AVICEL® PH-200 performed best. [ABSTRACT FROM AUTHOR]

Local chemotherapy using polymer drug delivery systems has the potential to treat some cancers, including intraocular retinoblastoma, which is difficult to treat with systemically delivered drugs. Well-designed carriers can provide the required drug concentration at the target site over a prolonged time, reduce the overall drug dose needed, and suppress severe side effects. Herein, nanofibrous carriers of the anticancer agent topotecan (TPT) with a multilayered structure composed of a TPT-loaded inner layer of poly(vinyl alcohol) (PVA) and outer covering layers of polyurethane (PUR) are proposed. Scanning electron microscopy showed homogeneous incorporation of TPT into the PVA nanofibers. HPLC-FLD proved the good loading efficiency of TPT (≥85%) with a content of the pharmacologically active lactone TPT of more than 97%. In vitro release experiments demonstrated that the PUR cover layers effectively reduced the initial burst release of hydrophilic TPT. In a 3-round experiment with human retinoblastoma cells (Y-79), TPT showed prolonged release from the sandwich-structured nanofibers compared with that from a PVA monolayer, with significantly enhanced cytotoxic effects as a result of an increase in the PUR layer thickness. The presented PUR-PVA/TPT-PUR nanofibers appear to be promising carriers of active TPT lactone that could be useful for local cancer therapy. [ABSTRACT FROM AUTHOR]

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The release kinetics of afobazole from a new solid dosage form of prolonged-release film-coated tablets was studied in vitro. The conditions of the dissolution test were experimentally determined with the use of the basket apparatus type I and phosphate buffer solution pH 6.8 (Eur. Ph.) as the dissolution medium. The specification release limits were ≤25% after 1 h, 45 – 60% after 6 h, and ≥80% after 24 h of the nominal afobazole content in the tablets. The release kinetics of afobazole from the prolonged-release tablets were evaluated using the first-order, Higuchi, and Korsmeyer(Peppas mathematical models. The release mechanism of the active ingredient from the matrix could be characterized as anomalous diffusion according to the Korsmeyer(Pappas model. [ABSTRACT FROM AUTHOR]

The focus of the current work is to study and demonstrate the impact of the design, the scale, and settings of fluid-bed coating equipment on the differences in pellet coating thickness, which in case of prolonged-release pellets dictates the drug release. In the first set of coating experiments, the pellet cores were coated with the Tartrazine dye with the aim of estimating the coating equipment performance in terms of coating thickness distribution, assessed through color hue. In the second set, drug-layered pellets were film-coated with prolonged-release coating and dissolution profile tests were performed to estimate the thickness and uniformity of the coating thickness among differently sized pellets. In both study parts, film coating was performed at the laboratory and the pilot scale and essentially two types of distribution plate and different height adjustments of the draft tube were compared. The dye coating study proved to be extremely useful, as the results enable process correction and the optimal use of the process equipment in combination with the appropriate process parameters. Preferential film coating of larger drug-containing pellets was confirmed on the laboratory scale, while on the pilot scale, it was possible to achieve preferential coating of smaller pellets using rational alternatives of settings, which is desirable in terms of particle size-independent drug release profile of such prolonged-release dosage forms. [ABSTRACT FROM AUTHOR]

Allapinin has antiarrhythmic activity and can be used to prevent and treat various supraventricular and ventricular arrhythmias. Nevertheless, it is highly toxic and has a number of side effects associated with non-specific accumulation in various tissues. The complex of this substance with the monoammonium salt of glycyrrhizic acid (Al:MASGA) has less toxicity and improved antiarrhythmic activity. However, the encapsulation of Al:MASGA in polyelectrolyte microcapsules (PMC) for prolonged release will reduce the residual adverse effects of this drug. In this work, the possibility of encapsulating the allapinin–MASGA complex in polyelectrolyte microcapsules based on polyallylamine and polystyrene sulfonate was investigated. The encapsulation methods of the allapinin–MASGA in polyelectrolyte microcapsules by adsorption and coprecipitation were compared. It was found that the coprecipitation method did not result in the encapsulation of Al:MASGA. The sorption method facilitated the encapsulation of up to 80% of the original substance content in solution in PMC. The release of the encapsulated substance was further investigated, and it was shown that the release of the encapsulated Al:MASGA was independent of the substance content in the capsules, but at pH 5, a two-fold decrease in the rate of drug release was observed.

Background: Meltdose tacrolimus (Envarsus®) has been marketed as a formulation achieving a more consistent tacrolimus exposure. Due to the narrow therapeutic window of tacrolimus, dose individualization is essential. Relaxation of the upper age limits for kidney transplantations has resulted in larger numbers of elderly patients receiving tacrolimus. However, due to the physiological changes caused by aging, the tacrolimus pharmacokinetics (PK) might be altered. The primary aim was to develop a population PK model in elderly kidney transplant recipients. Secondary aims were the development and evaluation of a limited sampling strategy (LSS) for AUC estimation. Methods: A total of 34 kidney transplant recipients aged ≥65 years, starting on meltdose tacrolimus directly after transplantation, were included. An eight-point whole blood AUC0–24h and an abbreviated dried blood spot (DBS) AUC0–24h were obtained. The PK data were analyzed using nonlinear mixed effect modeling methods. Results: The PK data were best described using a two-compartment model, including three transit compartments and a mixture model for oral absorption. The best three-sample LSS was T = 0, 2, 6 h. The best four-sample LSSs were T = 0, 2, 6, 8 h and T = 0, 1, 6, 8 h. Conclusions: The developed population PK model adequately described the tacrolimus PK data in a population of elderly kidney transplant recipients. In addition, the developed population PK model and LSS showed an adequate estimation of tacrolimus exposure, and may therefore be used to aid in tacrolimus dose individualization.

Local drug delivery systems are an effective approach in the treatment of purulent–septic inflammation of bone tissue. Chemically bonded multiphase ceramics based on calcium-deficient carbonate-substituted hydroxyapatite combine resorbability, osteoconductivity, and the possibility of volumetric incorporation of antibiotics. Macroporosity is regulated by the concentration of polyethylene glycol granules introduced into the initial powder composition, followed by their extraction. The selected conditions for the consolidation of the ceramic matrix and the extraction of PEG granules retain the activity of vancomycin, which is confirmed by the results of microbiological studies. The concentration of vancomycin and the porosity affect the local concentration and release of the antibiotic. The incorporation method provides a prolonged release of the antibiotic for up to 31 days. In vivo experiments with bone implantation have shown that chemically bound macroporous ceramics with incorporated vancomycin are a therapeutically effective carrier of the substance during the healing of bone defects in conditions of surrounding purulent–septic inflammation, and can be considered as a carrier for local antibacterial therapy, at the site of implantation.

(1) Background: this article investigates which PK metrics in a single-dose study (concentration at the end of posology interval, Cτ, partial areas under the curve, pAUCs, or half-value duration, HVD) are more sensitive and less variable for predicting the failure of a prolonged-release product at steady-state that was the bioequivalent for Cmax, AUC0-t and AUC0-inf, in the single-dose study; (2) Methods: a cross-over study was performed in 36 subjects receiving desvenlafaxine 100 mg prolonged-release tablets. Conventional (Cmax, AUC0-t and AUC0-inf) and additional (Cτ, pAUCs and HVD) PK metrics were considered after single-dose conditions. Predicted PK metrics at steady state (AUC0-τ, Cmax,ss, and Cτ,ss) were derived using a population PK model approach; (3) Results: the existing differences in the shape of the concentration–time curves precluded to show equivalence for Cτ,ss in the simulated study at steady state. This failure to show equivalence at steady state was predicted by Cτ, pAUCs and HVD in the single-dose study. Cτ was the most sensitive metric for detecting the different shape, with a lower intra-subject variability than HVD; (4) Conclusions: conventional PK metrics for single-dose studies (Cmax, AUC0-t and AUC0-inf) are not enough to guarantee bioequivalence at steady state for prolonged-release products. [ABSTRACT FROM AUTHOR]

We have investigated delivery systems that can form a structured matrix film on the skin after their application. In a previous work, we have shown that Weblike film forming systems (also called Pouches Drug Delivery Systems, PDDS) enable enhanced skin delivery of the incorporated molecules. These delivery systems are composed of one or more phospholipids, a short-chain alcohol, a polymer and optionally water. In this work, we continue the investigation and characterization of Weblike carriers focusing on some factors affecting the delivery properties such as components concentration and mode of application on the skin. Upon non-occluded application on the skin, the systems dry rapidly, forming a web-like structured film. Lidocaine, Ibuprofen, FITC and Cannabidiol are molecules with various physico-chemical properties that were incorporated in the carrier. The systems were tested in a number of in vitro and in vivo experiments. Results of the in vitro permeation of Ibuprofen through porcine skin indicated two-fold delivery through the skin of Ibuprofen when applied from our Weblike system in comparison with a nanovesicular carrier, the ethosome. We also have investigated weblike systems containing hemp seed oil (HSO). This addition enhanced the film's ability to deliver lipophilic molecules to the deeper skin layers, leading to an improved pharmacodynamic effect. In analgesic tests carried out in a pain mice model following one hour application of CBD in Weblike system with and without HSO, the number of writhing episodes was decreased from 29 in the untreated animals to 9.5 and 18.5 writhes, respectively. The results of our work open the way towards a further investigation of Weblike film forming systems containing drugs for improved dermal and transdermal treatment of various ailments. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) and its complications are one of the leading causes of death worldwide, with approximately 700 million people expected to suffer from DM by 2045, according to the International Diabetes Federation. DM is a progressive, chronic disease that affects various body systems and can lead to serious physical health complications. Type 2 diabetes mellitus (T2DM) has been shown to be associated with a higher incidence of sleep disturbances, which may be due to the disease itself or secondary complications or comorbidities associated with DM. However, epidemiological evidence suggests a higher risk of obesity, metabolic syndrome, and T2DM in individuals with shorter sleep duration and poor quality of sleep. Therefore, an assessment of the quality of sleep, its disorders and their pharmacological correction is recommended as a comprehensive medical examination for existing T2DM and for groups at risk of its development. Among pharmacotherapeutic agents for the treatment of sleep disorders, melatonin (N-acetyl-5-methoxytryptamine) attracts special attention. It is indoleamine, a pineal hormone synthesized in the human body, which name is related to the ability to aggregate melanin pigment granules. It has been found that melatonin directly participates in many biological processes and limits oxidative stress both extracellularly and intracellularly. Endogenous melatonin has linear kinetics, the half-life of the usual form of melatonin with rapid release ranges from 45 to 65 minutes, it is quickly metabolized and is completely excreted after 3–4 hours. Currently, 1 and 2 mg prolonged-release forms of melatonin are available, which provide slower and longer absorption, a delayed and lower peak dose, and levels maintained for 8 to 10 hours — similar to the physiological secretion curve of endogenous melatonin. Since the dose of melatonin in prolonged-release forms is much lower than in immediate release forms, this will help reduce the risk of possible side effects, including in patients with T2DM and in groups at risk of its development. [ABSTRACT FROM AUTHOR]

[Display omitted] The objective of this study was to evaluate the potential of novel poloxamer thermosensitive hydrogels (PTHs) formulations for prolonged release of iron dextran particles (IDP) for intramuscular (IM) injection. The thermosensitive behaviour helps to avoid hepcidin overexpression and toxicity by releasing IDPs without iron accumulation in injection or deposit sites. We hypothesized that novel PTH formulation would prolong iron liberation compared to the commercial iron dextran formulation (FEDEX). PTHs loaded with IDPs were developed with increasing iron content (0.1, 0.2 and 0.4 g of iron/g of poloxamer) and characterized as a prolonged release IM iron supplement. The PTHs had a biocompatible pH for IM injection (6.4) and thermosensitive viscosity, increasing from ∼50 (4 °C) to ∼3000 mPa.s (37 °C). PTHs were successfully injected in the sol state (at 4 °C) into pork meat at 37 °C, transitioning to the gel state in situ (in ∼60–190 s). Structural characterization indicated that there were no PTH-IDP chemical interactions, suggesting that IDP entrapment in PTHs was physical upon gelation. In vitro release studies revealed that iron release from PTH (0.4 g of iron/g of poloxamer) reached 100 % by day 10, whereas 100 % release from FEDEX was complete in 4 h. This novel iron PTH formulation achieved a 60 times long iron release compared to the commercial product. In conclusion, the reported strategy shows adequate IDP entrapment/release properties for prolonged iron release following ex vivo IM injection using biocompatible materials. These results provide a strong basis for future preclinical evaluation to elucidate aspects such as drug release, local irritation, biocompatibility, and efficacy. [ABSTRACT FROM AUTHOR]

Local drug delivery systems are an effective approach in the treatment of purulent–septic inflammation of bone tissue. Chemically bonded multiphase ceramics based on calcium-deficient carbonate-substituted hydroxyapatite combine resorbability, osteoconductivity, and the possibility of volumetric incorporation of antibiotics. Macroporosity is regulated by the concentration of polyethylene glycol granules introduced into the initial powder composition, followed by their extraction. The selected conditions for the consolidation of the ceramic matrix and the extraction of PEG granules retain the activity of vancomycin, which is confirmed by the results of microbiological studies. The concentration of vancomycin and the porosity affect the local concentration and release of the antibiotic. The incorporation method provides a prolonged release of the antibiotic for up to 31 days. In vivo experiments with bone implantation have shown that chemically bound macroporous ceramics with incorporated vancomycin are a therapeutically effective carrier of the substance during the healing of bone defects in conditions of surrounding purulent–septic inflammation, and can be considered as a carrier for local antibacterial therapy, at the site of implantation. [ABSTRACT FROM AUTHOR]

Nanocarriers for oxygen delivery have been the focus of extensive research to ameliorate the therapeutic effects of current anti-cancer treatments and in the organ transplant field. In the latter application, the use of oxygenated cardioplegic solution (CS) during cardiac arrest is certainly beneficial, and fully oxygenated crystalloid solutions may be excellent means of myocardial protection, albeit for a limited time. Therefore, to overcome this drawback, oxygenated nanosponges (NSs) that can store and slowly release oxygen over a controlled period have been chosen as nanocarriers to enhance the functionality of cardioplegic solutions. Different components can be used to prepare nanocarrier formulations for saturated oxygen delivery, and these include native α-cyclodextrin (αCD), αcyclodextrin-based nanosponges (αCD-NSs), native cyclic nigerosyl-nigerose (CNN), and cyclic nigerosyl-nigerose-based nanosponges (CNN-NSs). Oxygen release kinetics varied depending on the nanocarrier used, demonstrating higher oxygen release after 24 h for NSs than the native αCD and CNN. CNN-NSs presented the highest oxygen concentration (8.57 mg/L) in the National Institutes of Health (NIH) CS recorded at 37 °C for 12 h. The NSs retained more oxygen at 1.30 g/L than 0.13 g/L. These nanocarriers have considerable versatility and the ability to store oxygen and prolong the amount of time that the heart remains in hypothermic CS. The physicochemical characterization presents a promising oxygen-carrier formulation that can prolong the release of oxygen at low temperatures. This can make the nanocarriers suitable for the storage of hearts during the explant and transport procedure.

This study aimed to develop a prolonged-release system based on palygorskite and chitosan, which are natural ingredients widely available, affordable, and accessible. The chosen model drug was ethambutol (ETB), a tuberculostatic drug with high aqueous solubility and hygroscopicity, which is incompatible with other drugs used in tuberculosis therapy. The composites loaded with ETB were obtained using different proportions of palygorskite and chitosan through the spray drying technique. The main physicochemical properties of the microparticles were determined using XRD, FTIR, thermal analysis, and SEM. Additionally, the release profile and biocompatibility of the microparticles were evaluated. As a result, the chitosan–palygorskite composites loaded with the model drug appeared as spherical microparticles. The drug underwent amorphization within the microparticles, with an encapsulation efficiency greater than 84%. Furthermore, the microparticles exhibited prolonged release, particularly after the addition of palygorskite. They demonstrated biocompatibility in an in vitro model, and their release profile was influenced by the proportion of inputs in the formulation. Therefore, incorporating ETB into this system offers improved stability for the administered product in the initial tuberculosis pharmacotherapy dose, minimizing its contact with other tuberculostatic agents in the treatment, as well as reducing its hygroscopicity.

Transdermal drug delivery systems (TDDSs) were developed for prolonged tamsulosin (TMS) delivery. Double layer (DL) TDDSs were prepared using Eudragit® RL by conventional film-forming. Ethylene-vinyl acetate was used as the backing layer, triethylcitrate as plasticizer, and Capmul® PG-8-70 NF and Captex 170 EP as penetration enhancers (PEs). An increase in either drug or PE concentration caused a significant increase in drug permeation flux. Modulation of drug permeation across Strat-M® membrane was examined using a single layer (SL) having the same thickness and drug content as the DLs, while the DLs were formulated to have variable drug spatial distribution across each layer (DL 4:6 and DL 6:4). SL/TDDS showed significantly higher daily drug permeation than DL/TDDSs for the first 4 days which could be related to the presence of high TMS concentration located on the upper surface of SL/TDDS as a result of solute migration of TMS during the drying process. However, this increase was followed by a progressive linear decrease after 5 days. Deflection points that were characterized by lower drug flux had been shown by SL/TDDS at more than one-point times. In contrast, DL 4:6 and DL 6:4 TDDSs demonstrated an ability to sustain TMS delivery for up to 2 weeks. [ABSTRACT FROM AUTHOR]

• Development of a biocompatible magnetic material with MOF coating. • Enhanced drug loading efficiency achieved through an optimized SSI process. • Prolonged drug release behavior with a good model fit. In this study, core–shell structured Fe 3 O 4 @MIL-100 nanoparticles were synthesized through an in-situ growth method. The resulting magnetic composite exhibited significant magnetic responsivity, with a magnetization saturation (Ms) of 37.24 emu/g and a magnetocaloric temperature rise of 42.1 ℃ within 6 min at 20 A. Supercritical solution impregnation (SSI) technology was used for CUR loading, achieving an outstanding drug loading content of 4.36 wt% compared to ethanol impregnation. These results show the potential of the present magnetic materials with SSI process in biomedical applications. [ABSTRACT FROM AUTHOR]

Local chemotherapy using polymer drug delivery systems has the potential to treat some cancers, including intraocular retinoblastoma, which is difficult to treat with systemically delivered drugs. Well-designed carriers can provide the required drug concentration at the target site over a prolonged time, reduce the overall drug dose needed, and suppress severe side effects. Herein, nanofibrous carriers of the anticancer agent topotecan (TPT) with a multilayered structure composed of a TPT-loaded inner layer of poly(vinyl alcohol) (PVA) and outer covering layers of polyurethane (PUR) are proposed. Scanning electron microscopy showed homogeneous incorporation of TPT into the PVA nanofibers. HPLC-FLD proved the good loading efficiency of TPT (≥85%) with a content of the pharmacologically active lactone TPT of more than 97%. In vitro release experiments demonstrated that the PUR cover layers effectively reduced the initial burst release of hydrophilic TPT. In a 3-round experiment with human retinoblastoma cells (Y-79), TPT showed prolonged release from the sandwich-structured nanofibers compared with that from a PVA monolayer, with significantly enhanced cytotoxic effects as a result of an increase in the PUR layer thickness. The presented PUR-PVA/TPT-PUR nanofibers appear to be promising carriers of active TPT lactone that could be useful for local cancer therapy.

Solid dosage forms based on hypromellose (HPMC) with prolonged/extended drug release are very important from the research and industrial viewpoint. In the present research, the influence of selected excipients on carvedilol release performance from HPMC-based matrix tablets was studied. A comprehensive group of selected excipients was used within the same experimental setup, including different grades of excipients. Compression mixtures were directly compressed using constant compression speed and main compression force. LOESS modelling was used for a detailed comparison of carvedilol release profiles via estimating burst release, lag time, and times at which a certain % of carvedilol was released from the tablets. The overall similarity between obtained carvedilol release profiles was estimated using the bootstrapped similarity factor (f2). In the group of water-soluble carvedilol release modifying excipients, which produced relatively fast carvedilol release profiles, POLYOXᵀᴹ WSR N-80 and Polyglykol® 8000 P demonstrated the best carvedilol release control, and in the group of water-insoluble carvedilol release modifying excipients, which produced relatively slow carvedilol release profiles, AVICEL® PH-102 and AVICEL® PH-200 performed best.

Modeling of metabolite kinetics after oral administration of ketamine is of special interest because of the higher concentrations of active metabolites because of the hepatic first‐pass effect. This holds especially in view of the potential analgesic and antidepressant effects of 2R,6R‐ and 2S,6S‐hydroxynorketamine at low doses of ketamine. Therefore, a 9‐compartment model was developed to analyze the pharmacokinetics of ketamine enantiomers and their metabolites after racemic ketamine administered intravenously (5 mg) and as 4 doses (10, 20, 40, and 80 mg) of a prolonged‐release formulation (PR‐ketamine). Using a population approach, the serum concentration‐time data of the enantiomers of ketamine, norketamine, dehydronorketamine, and 2,6‐hydroxynorketamine obtained in 15 healthy volunteers could be adequately fitted. The estimated model parameters were used to simulate serum concentration‐time profiles; after multiple dosing of PR‐ketamine (2 daily doses of 20 mg), the steady‐state concentrations of R‐ and S‐ketamine were 1.4 and 1.3 ng/mL, respectively. The steady‐state concentration of 2R,6R‐hydroxynorketamine exceeded those of R‐norketamine (4‐fold), R‐dehydonorketamine (8‐fold), and R‐ketamine (46‐fold), whereas that of 2S,6S‐hydroxynorketamine exceeded that of S‐ketamine by 14‐fold. The model may be useful for identifying dosing regimens aiming at optimal plasma concentrations of 2,6‐hydroxynorketamines. [ABSTRACT FROM AUTHOR]

[Display omitted] For binder-free dry particulate coating to prepare controlled-release micron-sized particles, we designed nanocomposite coating agents with the intention to form a core-shell structure composed of two types of acrylic polymers with different glass transition temperatures (Tg) and evaluated their coating performance. A series of nanocomposite acrylic latexes synthesized by emulsion polymerization was freeze-dried after salting-out to create the powder form. An ion-exchange resin loaded with diclofenac sodium (DS, a model drug) (IER-DS) with a median diameter of approximately 100 µm was used as the core particle. Dry coating of the IER-DS with nanocomposite coating agents was carried out using a laboratory-made coating apparatus assisted with mild-intensity vibration and zirconia bead impaction. The coated particles were cured by heating at a temperature 20 °C higher than the Tg for 12 h to complete the film-forming process. It was found that the highest coating efficiency (more than 70%) and a remarkably prolonged release period of the drug (the time required for 50% release reached approximately 12 h) could be achieved when nanocomposite coating agents with a soft polymeric core (Tg = 30 °C) and a hard polymeric shell (Tg = 80 °C) were applied. In contrast, nanocomposite coating agents with a combination of a hard polymeric core and a soft polymeric shell resulted in lower coating efficiency. These results demonstrate that nanocomposite polymeric coating agents composed of a soft core and a hard shell are effective for the production of drug-loaded microparticles with a prolonged release function by a binder-free dry-coating process. [ABSTRACT FROM AUTHOR]

(1) Background: this article investigates which PK metrics in a single-dose study (concentration at the end of posology interval, Cτ, partial areas under the curve, pAUCs, or half-value duration, HVD) are more sensitive and less variable for predicting the failure of a prolonged-release product at steady-state that was the bioequivalent for Cmax, AUC0-t and AUC0-inf, in the single-dose study; (2) Methods: a cross-over study was performed in 36 subjects receiving desvenlafaxine 100 mg prolonged-release tablets. Conventional (Cmax, AUC0-t and AUC0-inf) and additional (Cτ, pAUCs and HVD) PK metrics were considered after single-dose conditions. Predicted PK metrics at steady state (AUC0-τ, Cmax,ss, and Cτ,ss) were derived using a population PK model approach; (3) Results: the existing differences in the shape of the concentration–time curves precluded to show equivalence for Cτ,ss in the simulated study at steady state. This failure to show equivalence at steady state was predicted by Cτ, pAUCs and HVD in the single-dose study. Cτ was the most sensitive metric for detecting the different shape, with a lower intra-subject variability than HVD; (4) Conclusions: conventional PK metrics for single-dose studies (Cmax, AUC0-t and AUC0-inf) are not enough to guarantee bioequivalence at steady state for prolonged-release products.

One of the mains factors affecting the effectiveness and safety of the therapy is the development of an appropriate dosage form adapted to the age of the patients and ease to administer as well as a dosing devices that provide flexible dosing. This approach is in accordance with the idea of patient-centered treatment. Given advantages such as safety, easy swallowing and flexible dose adjustment, special attention is paid to oral dosage forms such as orally disintegrating tablets, minitablets and orodispersible films (ODF). The ODF films are indicated as a suitable dosage form for pediatric, geriatric and uncooperative patients due to their fast disintegration in the mouth without need for water to facilitate swallowing, adhesion to the oral cavity to prevent spitting out the medicine and the ability to adjust the dose of the drug for an individual patient. According to many studies, orodispersible films are well accepted by infants and preschool children, their caregivers (nurses) and parents. They have the form of a postage stamp sized strip of thin polymeric film applied on the tongue. The ODF films can be manufactured using various methods, i.e. casting method, hot melt extrusion, electrospinning or printing (inkjet, flexographic and 3D printing) on an industrial scale and potentially in hospital pharmacies. Extemporaneous preparation of the ODF films create more dose flexibility affecting patient’s adherence to pharmacotherapy. Innovative solutions in this area concern also designed specifically devices for storage and dosing of ODF, as well as methods of labeling and identification of single doses, for example Quick Response (QR) codes. The paper presents a review of the literature from recent years regarding new technology in the terms of the ODF films preparation, including manufacturing methods and modification of the drug release, as well as the possibilities of their application in individualization of the therapy especially in pediatric and geriatric population.

The structure and diffusion properties of combined ultrafibrous matrices containing microspheres for prolonged release of lysozyme are studied in the work. The matrices are biocompatible and they are not cytotoxic. The matrices are obtained via electrospinning. These materials are suitable for solving problems of tissue engineering, since they combine ultrafine fibers of poly(hydroxybutyrate) promoting effective attachment and growth of cells and poly(hydroxybutyrate) microparticles capable of prolonged release of a bioactive compound. These properties allow one to recommend these matrices for tissue engineering. [ABSTRACT FROM AUTHOR]

There are no specific requirements and recommendations in the Russian Federation for evaluation of bioequivalence of modified-release medicinal products. Until recently, modified-release products were regulated in a similar manner as immediate-release products, which is unacceptable considering the active ingredient release profile and its pharmacokinetics. The modified release characteristics require a more complex approach to the assessment of equivalence of generic medicines as compared with the reference product. The number of parameters to be assessed and the scope of testing depend on many factors (release mechanism, specific features of the dosage form, linearity of pharmacokinetics, potential for ingredient accumulation, dependence on food intake, dose-dumping effects, and the number of dosage strengths to be registered). The aim of this paper was to develop recommendations for the national procedure of modified-release products authorisation based on the analysis of international regulatory experience in this field. The paper reviews the current European Medicines Agency (EMA) guidelines on evaluation of bioequivalence of generic modified-release dosage forms for oral use that were taken as a basis for the development of Eurasian Economic Union regulations on bioequivalence assessment. The analysis of the above-mentioned documents made it possible to develop recommendations for the national procedure of modified-release products authorisation. In the case of modified-release products for oral use it is recommended to perform bioequivalence studies by comparing the test product with the reference product. The authors developed a procedural algorithm for bioequivalence studies of modified-release medicinal products.

The aim of this research is to prepare and evaluate lignocaine HCl Proniosomal orabase for enhanced permeation and prolonged dental anaesthesia effect. Objective: Various lignocaine proniosomal gels were formulated employing various surfactants. Methods: The formulations were scrutinized for entrapment efficiency, optical microscopy, in-vitro diffusion and release studies, mucoadhesive strength, ex-vivo permeation studies and drug - excipient interactions were determined by FTIR spectroscopy. Results: span 80 was found to be superior and significant for loading in to orabase. Considering the best entrapment efficiency with span 80 (91.60%) and optimum vesicle shape, along with prolonged drug permeation (33.6% for 24 h) the formulation F4 was selected and optimized for loading into orabase. The formulation F4 loaded orabase exhibited significant prolonged release over 10 h, and permeation profiles exhibited nearly two - fold increased flux in comparison with control. Good mucoadhesive strength was observed for proniosomal orabase 6273dynes/cm2, No evidence of incompatibility amongst formulation components from FTIR studies. SEM images revealed the particle size range from 50 µmt to 100 µmt for proniosomal orabase. Conclusion: Orabase can be an effective carrier for proniosomes with enhanced retention time at the site of application and provide prolonged release for oro-dental conditions. [ABSTRACT FROM AUTHOR]

In this work, cashew apple pectin (CP) of the species Anacardium occidentale L. was used as an encapsulation matrix for hydrophobic drugs. The model drug chosen was mangiferin (Mf), a glycosylated C -xanthone which has antioxidant properties but low solubility in aqueous medium. CP (1–100 μg mL−1) was not toxic to human neutrophils and also did not significantly interfere with the pro-inflammatory mechanism of these cells in the concentration range of 12.5 and 100 μg mL−1. The results are promising because they show that pectin encapsulated mangiferin after spray drying presented an efficiency of 82.02%. The results obtained in the dissolution test, simulating the release of mangiferin in the gastrointestinal tract (pH 1.2, 4.6 and 6.8) and using Franz diffusion cells (pH 7.4), showed that cashew pectin may be a promising vehicle in prolonged drug delivery systems for both oral and dermal applications. Unlabelled Image [ABSTRACT FROM AUTHOR]

Objective of the study was to design an injectable microsphere preparation with high drug loading of bupivacaine for prolonged release and local anesthetic. PLA or PLGA was used as the biodegradable matrix material to fabricate microspheres with the o/w emulsification-solvent evaporation method. The characterization of bupivacaine microspheres was observed by SEM, DSC, and XRPD. The microsphere preparation and extended drug release, as well as the plasma drug concentration and sciatic nerve blockade after injection of the microsphere formulation to rats were investigated. High drug-loading microspheres of more than 70% were successfully obtained with extended drug release over 5 days in vitro depending on the type of matrix and the feed ratio of drug to polymer. SEM, DSC, and XRPD results verified a novel microsphere structure characterized as the porous core composed of PLA material and form II bupivacaine crystals and dense shell formed of PLA layer. The mechanism that bupivacaine was dissolved inside the microsphere and diffused across the dense shell was suggested for drug release in vitro. The optimized PLA microsphere formulation showed low and steady plasma drug concentration over 5 days and prolonged duration of sensory and motor blockade of sciatic nerve lasted more than 3 days. Results indicated that the porous core-shell structure of PLA microsphere formulation would provide enormous potential as an injectable depot for locally prolonged delivery of bupivacaine and control of postoperative pain. [ABSTRACT FROM AUTHOR]