Matrix Granules Research Articles

Application of Galenic Strategies for Developing Gastro-Resistant Omeprazole Formulation for Pediatrics.

This study addresses a critical need in pediatric pharmacotherapy by focusing on the development of an enteric formulation of omeprazole for pediatric use. Omeprazole, a widely used proton pump inhibitor, is essential for treating various gastrointestinal disorders in children. The main objective is to design a compounding formula that can be prepared in hospital pharmacy services without the need for industrial equipment, which is often unavailable in these settings. The research applied different galenic strategies to overcome the challenges of omeprazole's instability in acidic environments and its complex pharmacokinetic and physicochemical properties. The experiments were conducted sequentially, employing salting out, ionic gelation, and matrix granulation strategies. Based on the results obtained, the control conditions and parameters for the various trials were established. Among the techniques used, wet granulation proved to be the most promising, achieving a gastro-resistance level of 44%. In contrast, the ionic gelation and salting-out techniques did not yield satisfactory results. The findings of this study underscore the need to adopt alternative formulation strategies to ensure the stability of omeprazole. This goal requires a multidisciplinary approach and continuous effort to design omeprazole formulations that meet quality standards and appropriate gastro-resistance requirements.

Disruption of the mitochondrial network in a mouse model of Huntington's disease visualized by in-tissue multiscale 3D electron microscopy

Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the coding sequence of huntingtin protein. Initially, it predominantly affects medium-sized spiny neurons (MSSNs) of the corpus striatum. No effective treatment is still available, thus urging the identification of potential therapeutic targets. While evidence of mitochondrial structural alterations in HD exists, previous studies mainly employed 2D approaches and were performed outside the strictly native brain context. In this study, we adopted a novel multiscale approach to conduct a comprehensive 3D in situ structural analysis of mitochondrial disturbances in a mouse model of HD. We investigated MSSNs within brain tissue under optimal structural conditions utilizing state-of-the-art 3D imaging technologies, specifically FIB/SEM for the complete imaging of neuronal somas and Electron Tomography for detailed morphological examination, and image processing-based quantitative analysis. Our findings suggest a disruption of the mitochondrial network towards fragmentation in HD. The network of interlaced, slim and long mitochondria observed in healthy conditions transforms into isolated, swollen and short entities, with internal cristae disorganization, cavities and abnormally large matrix granules.

Simultaneous assessment of absorption and pharmacokinetic characteristics of four active flavonoids from Chimonanthus nitens Leaf Granules using LC-MS determination: in vivo and in vitro

A sensitive UPLC-HRMS method was developed and validated for simultaneous quantification of four active flavonoids from Chimonanthus nitens Leaf Granules (CNLG) in biological matrix. The method was utilized in pharmacokinetic study of the four flavonoids in rats as well as other evaluation assays in vitro. It was revealed that rutin, nicotiflorin, and astragalin had poor oral bioavailability in rats possibly due to low intestinal permeability and metabolism in intestinal flora. Kaempferol underwent rapid glucuronidation and sulphation in rat plasma with medium permeability coefficient. The results provided valuable data for future research and development of CNLG flavonoids.

Variation in the Floral Scent Chemistry of Nymphaea 'Eldorado', a Valuable Water Lily, with Different Flowering Stages and Flower Parts.

Nymphaea 'Eldorado', a valuable water lily, is a well-known fragrant plant in China. Studying the temporal and spatial characteristics of the floral components of this plant can provide a reference for the further development and utilization of water lily germplasm resources. In this study, headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS) was used to explore the types and relative contents of floral components at different flowering stages (S1: bud stage; S2: initial-flowering stage; S3: full-flowering stage; S4: end-flowering stage) and in different floral organs of N. 'Elidorado', combined with the observation of the microscopic structure of petals. A total of 60 volatile organic compounds (VOCs) were detected at different flowering stages, and there were significant differences in floral VOCs at different flowering stages and in different flower organs. The volatile compounds of N. 'Eldorado' can be divided into seven chemical classes,, namely, alkenes, alcohols, esters, aldehydes, ketones, alkanes, and others; the most common were alkenes and alkanes. A total of 39, 44, 47, and 42 volatile compounds were detected at S1, S2, S3, and S4. The VOCs present in high concentrations include benzaldehyde, benzyl alcohol, benzyl acetate, trans-α-bergamotene, α-curcumene, cis-α-farnesene, and so on. The types and total contents of volatiles at the full-flowering stage were higher than at other flowering stages. Comparing the VOCs in different parts of flower organs, it was found that the contents of alcohols, esters, and aldehydes were greatest in the petals, the alkenes in stamens were abundant with a relative content of up to 54.93%, and alkanes in the pistil were higher than in other parts. The types and total contents of volatiles in the stamens of N. 'Eldorado' were higher than those in other flower organs; they were the main part releasing fragrance. The observation of petal microstructure revealed that the size and quantity of the papillae on the epidermises of petals, the number of intracellular plastids, and the aggregates of floral components (osmophilic matrix granules) were significantly higher at the full-flowering stage than at the other flowering stages. This study suggested the main flowering stage and location at which the floral VOCs are released by N. 'Eldorado' and provided a reference for guiding the breeding of this water lily, exploring genetic patterns and developing related products.

Open-Circuit Fault Diagnosis of T-Type Three-Level Inverter Based on Knowledge Reduction

Compared with traditional two-level inverters, multilevel inverters have many solid-state switches and complex composition methods. Therefore, diagnosing and treating inverter faults is a prerequisite for the reliable and efficient operation of the inverter. Based on the idea of intelligent complementary fusion, this paper combines the genetic algorithm–binary granulation matrix knowledge-reduction method with the extreme learning machine network to propose a fault-diagnosis method for multi-tube open-circuit faults in T-type three-level inverters. First, the fault characteristics of power devices at different locations of T-type three-level inverters are analyzed, and the inverter output power and its harmonic components are extracted as the basis for power device fault diagnosis. Second, the genetic algorithm–binary granularity matrix knowledge-reduction method is used for optimization to obtain the minimum attribute set required to distinguish the state transitions in various fault cases. Finally, the kernel attribute set is utilized to construct extreme learning machine subclassifiers with corresponding granularity. The experimental results show that the classification accuracy after attribute reduction is higher than that of all subclassifiers under different attribute sets, reflecting the advantages of attribute reduction and the complementarity of different intelligent diagnosis methods, which have stronger fault-diagnosis accuracy and generalization ability compared with the existing methods and provides a new way for hybrid intelligent diagnosis.

İZOSORBİD DİNİTRATIN MODİFİYE SALIM YAPAN ÇOK BİRİMLİ BİLEŞİMİNİN TABLET ŞEKLİNDE BASILMASI VE DEĞERLENDİRİLMESİ

Objective: This study was aimed to create a multiple-unit dosage form of isosorbide dinitrate by pressing spherical matrix granules into tablets, selecting the optimal technology parameters and evaluating the obtained tablets. Material and Method: The tablet cores were prepared from mixtures of active matrix granules and shock-absorbing auxiliary granules in various ratios using diverse tabletting forces. The dissolution profiles of the obtained tablet compositions were evaluated in comparison with the reference preparation. Result and Discussion: An optimal ratio of spheroids with the active component with auxiliary granules along with optimal compression parameters were determined. The resulting as multiple-unit tablets exhibited a release profile similar to that of Cardicket Retard. Used technological approach makes it possible to regulate the dissolution profile of tablets by changing the ratio of active granules with different kinetics of the active substance release.

Effect of Addition of Cross-Linked Starch on the Properties of Degraded PBAT Poly(butylene adipate-co-terephthalate) Films.

This work aimed to evaluate the properties of butylene adipate-co-terephthalate (PBAT) degraded after 1800 days of storage (DPBAT) by preparing blends (films) with crosslinked starch (Cm) through extrusion and thermocompression. Different ratios of DPBAT:Cm (70:30, 60:40, and 50:50 m/m) were prepared. The incorporation of Cm into DPBAT significantly changed the properties of the films by making them stiffer (increasing Young's modulus by up to 50%) and increasing the thermal resistance of DPBAT. The presence of crosslinked starch in the films made them less hydrophobic (with decreased contact angle and increased moisture content), but these parameters did not vary linearly with changes in the content of crosslinked starch in the blend (DPBAT:Cm). The microscopic images show an inhomogeneous distribution of Cm granules in the DPBAT matrix. Thus, the films prepared with PBAT show a significant decrease in their mechanical parameters and heat resistance after long-term storage. However, the preparation of blends of degraded DPBAT with crosslinked starch promoted changes in the properties of the films prepared by thermocompression, which could be useful for disposable packaging.

Comparison of Different Aerogel Granules for Use as Aggregate in Concrete

In previous work of this group, a structural lightweight concrete was developed by embedding silica aerogel granules in a high-strength cement matrix. This concrete, called high-performance aerogel concrete (HPAC), is a lightweight building material characterized by its simultaneous high compressive strength and very low thermal conductivity. Besides these features, high sound absorption, diffusion permeability, water repellence and fire resistance qualify HPAC as an interesting material for the construction of single-leaf exterior walls without any further insulation. During the development of HPAC, the type of silica aerogel was found to majorly influence both fresh and hardened concrete properties. To clarify these effects, a systematic comparison of SiO2 aerogel granules with different levels of hydrophobicity as well as different synthesis methods was conducted in the present study. The granules were analyzed for their chemical and physical properties as well as their compatibility in HPAC mixtures. These experiments included determinations of pore size distribution, thermal stability, porosity, specific surface and hydrophobicity, as well as fresh/hardened concrete experiments such as measurements of compressive strength, flexural bending strength, thermal conductivity and shrinking behavior. It was found that the type of aerogel has a major influence on the fresh and hardened concrete properties of HPAC, particularly compressive strength and shrinkage behavior, whereas the effect on thermal conductivity is not very pronounced.

Skeletal Network Enabling New-Generation Thermoplastic Vulcanizates.

Upcycling of cross-linked rubbers is pressing. The introduction of dynamic covalent bonds into the networks is a popular tactic for recycling thermosetting polymers, but it is very challenging to integrate engineering performance and continuous yet stable reprocessability. Based on traditional rubber formulations, herein, a straightforward strategy is presented for constructing a skeletal network (SN) through interfacial cross-linking and percolation of rubbery granules in a rubber matrix. Rapid exchange reactions involving dynamic interfacial sulfides realize repeated "fragmentation and healing" in the solid-state and consequent reconfiguration of the SN topology of the elastomer, thus endowing the resultant SN elastomer with continuous yet stable re-extrudability. These SN elastomers with hierarchical structures exhibit high gel contents, high resilience, low creep, and reinforcibility competitive to traditional vulcanizates. Specifically, SN elastomers exhibit better overall performance than commercial thermoplastic vulcanizates (TPVs) materials. Overall, a new concept of thermoplastic vulcanizates is proposed, which will promote the sustainable development of rubbers. This article is protected by copyright. All rights reserved.

Tooth-Derived Matrix Granules for Enhanced Bone Healing: Chemical Composition, Morphological Aspects, and Clinical Outcomes

Bone grafting has increasingly been used in surgical procedures for enhanced bone augmentation. Tooth-derived graft material has received considerable attention due to its chemical composition and autogenous source that can improve bone tissue healing. The main aim of this study was to provide a short and comprehensive review on the chemical composition, morphological aspects, and clinical outcomes of bone grafting using tooth-derived matrix granules. Dentin tissue has a chemical composition similar to that on bone tissues regarding the presence of hydroxyapatite, type I collagen, and different growth factors. Dentin-matrix granules are often processed at well-controlled size ranging from approximately 300 up to 1300 µm, while maintaining porosity and organic content. In addition, a dense collagen fiber network is still present after the milling and chemical treatment of dentin granules. Thus, dentin-matrix granules can improve the bone healing process considering their chemical composition, porous structure, and adequate size. However, further in vivo and in vitro studies should be performed taking into consideration different demineralization procedures, remnant organic content, porosity, and granule size.

IL1β/ TNFα/COX-2/VEGF axis responsible for effective healing potential of C-glucoside xanthone (mangiferin) based ointment in immunocompromised rats

Present study was conducted to undermine the wound healing potential of mangiferin vis a vis its molecular dynamics in immunocompromised excisional rat model. 120 rats were randomly and equally divided into five groups viz. group I (Healthy control), group II (Immunocompromised control), group III (Immunocompromised group treated with silver sulphadiazine), group IV (Immunocompromised group treated with 2.5 %Mangiferin) and group V (Immunocompromised group treated with 5 %Mangiferin). Immuno compromised state was achieved following intramuscular injection of Hydrocortisone @ 80 mg/kg body weight. Study was conducted for a period of 28 days. Six animals from each group were humanely sacrificed at weekly interval till day 28th of study. Planimetric analysis, biochemical studies viz. hydroxyproline assay, total protein and DNA content, antioxidative potential through LPO assay was done along with molecular studies involving expression profiling of IL1β, TNFα and COX-2 and Immunohistochemistry of angiogenic marker i.e. VEGF was performed to undermine the pharmacodynamics of mangiferin. Histopathological studies including H&E and Masson’s Trichome was also performed to study histoarchitectural changes in wound healing and reparative process following application of mangiferin ointment. Study revealed significant (P ≤ 0.05) reduction in wound area measurement and significant (P ≤ 0.05) increase in wound contraction (%) following mangiferin administration in immunocompromised rats. Hydroxyproline, DNA and total protein showed significant (P ≤ 0.05) increase in skin tissues of mangiferin treated immunocompromised rats. LPO assay revealed significant (P ≤ 0.05) reduction in mangiferin treated animals. Histopathological studies of skin tissues revealed complete restoration advocating grade III of healing in 2.5% mangiferin treated group. Higher expression and strong signal intensity of VEGF was noticed in 2.5% mangiferin treatment group along with significant (P ≤ 0.05) upregulation IL1β and TNFα on day 7 in 2.5% mangiferin treatment group with significant (P ≤ 0.05) down regulation of COX-2 in mangiferin treatment group as compared to other groups i.e. group II and III. It is concluded from our study that mangiferin facilitates wound healing through improved wound closure, organized deposition of collagen deposition and granulation matrix formation.

A Novel Manufacturing Process for Nanosilica Carbide Reinforced Al2024 Matrix Composites

Fabrication of SiC nanoparticle enhanced Al2024 composite material with near-net form SiC nano particles is discussed in this research using the flake powder metallurgy (PM) technique. Analysis of particle size and quantity of Silicon Carbide (SiC) nanoparticles in flake Al2024 matrix granules along with their effect on particle distribution, structure, relative compactness, and hardness were conducted. The granules Al2024 substrate particles were combined to 3 various size of some as Al2024 powders using a ball milling process. With intergranular wide enough to incorporate reinforcements, the Al2024 matrix powders were discovered to have flake-like microstructures with distributed SiC nanoparticles spread throughout. Hot pressed density raised as a result of the slight frictional forces among the thin flake elements. The rigidity of Aluminium Alloy 2021/Silicon carbide nanocomposites was employed to expand the size of matrix particles.

Preparation and characterization of Cu-GO and Cu-GO-YSZ nanocomposite coating by electrochemical deposition for improved mechanical and anti-corrosion properties

Graphene oxide (GO) and yttria-stabilized zirconia (YSZ) nanoparticle reinforced copper (Cu) matrix nanocomposite coatings were successfully fabricated via direct current electroplating from a copper sulfate electrolyte. Influences of particle concentration (GO/YSZ) in electrolyte, electrodeposition time and applied current density on composition, microstructural and anti-corrosion performance of Cu-GO and Cu-GO-YSZ composite coatings were explored. The corrosion behaviors were evaluated by electrochemical measurement. Results indicated the composite coatings exhibit a uniform and compact surface which was made up of stacked granules, exhibiting morphologies that nanoflake-like structures dispersed on the pyramid-like copper matrix granule clusters network. The crystallite sizes of Cu-GO first increased and then decreased as GO, time and current density increased, while it varied little for Cu-GO-YSZ composite coating. The preferred orientation of Cu matrix composite coating was oriented (220) texture. The content of incorporated GO increased with the introduction of YSZ into the Gu-GO matrix. The Gu-GO coating contains 93.3 wt% Cu and 5.5 GO, and the Gu-GO-YSZ coating contains 91.7 wt% Cu and 7.6 wt% GO. The average roughness Ra of Cu-GO and Cu-GO-YSZ were 240 ± 7 nm and 236 ± 40 nm, respectively. The addition of GO nanosheets could improve the microhardness and decrease the COF of Cu matrix. Both self-lubrication effect and load-bearing capability were improved by introducing GO and YSZ together in the Cu matrix. Deposits obtained at 30 mA cm−2, 30 min, 0.1 g L−1 GO and 10 g L−1 YSZ particles own the optimal corrosion resistance with the maximum Rp. It reveals that corrosion resistance was enhanced by the presence of GO nanosheets in Cu matrix for physical isolation effect of GO and the preferred orientation (220) plane, which benefited the formation of passive film.

Comparative Study of the Petal Structure and Fragrance Components of the Nymphaea hybrid, a Precious Water Lily.

Nymphaea hybrid, a precious water lily, is a widely-cultivated aquatic flower with high ornamental, economic, medicinal, and ecological value; it blooms recurrently and emits a strong fragrance. In the present study, in order to understand the volatile components of N. hybrid and its relationship with petals structure characteristics, the morphologies and anatomical structures of the flower petals of N. hybrid were investigated, and volatile compounds emitted from the petals were identified. Scanning and transmission electron microscopy were used to describe petal structures, and the volatile constituents were collected using headspace solid-phase microextraction (HS-SPME) fibers and analyzed using gas chromatography coupled with mass spectrometry (GC-MS). The results indicated that the density and degree of protrusion and the number of plastids and osmiophilic matrix granules in the petals play key roles in emitting the fragrance. There were distinct differences in the components and relative contents of volatile compounds among the different strains of N. hybrid. In total, 29, 34, 39, and 43 volatile compounds were detected in the cut flower petals of the blue-purple type (Nh-1), pink type (Nh-2), yellow type (Nh-3) and white type (Nh-4) of N. hybrid at the flowering stage, with total relative contents of 96.78%, 97.64%, 98.56%, and 96.15%, respectively. Analyses of these volatile components indicated that alkenes, alcohols, and alkanes were the three major types of volatile components in the flower petals of N. hybrid. The predominant volatile compounds were benzyl alcohol, pentadecane, trans-α-bergamotene, (E)-β-farnesene, and (6E,9E)-6,9-heptadecadiene, and some of these volatile compounds were terpenes, which varied among the different strains. Moreover, on the basis of hierarchical cluster analysis (HCA) and principal component analysis (PCA), the N. hybrid samples were divided into four groups: alcohols were the most important volatile compounds for Nh-4 samples; esters and aldehydes were the predominant volatiles in Nh-3 samples; and ketones and alkenes were important for Nh-2 samples. These compounds contribute to the unique flavors and aromas of the four strains of N. hybrid.

Development of High Performance Aerogel Concrete (HPAC) and statistical evaluation of compressive strength for practical use in construction

The Institute for Structural Concrete (ISC) at the University of Duisburg-Essen and the Institute of Materials Research of the German Aerospace Center (DLR) developed a new lightweight concrete, called “High Performance Aerogel Concrete” (HPAC). HPAC is made by embedding of silica aerogel granules in a high strength cement matrix. It exhibits a remarkable relation between compressive strength and thermal conductivity. HPAC for the load bearing layer of double-leaf external walls contains approx. 50 vol% aerogel and has a compressive strength in the range of normal concrete (20 MPa – 30 MPa). Up to now, the compressive strength of each mixture was determined on three to six cubes or cylinders. The scattering of the results has not been investigated yet. For this reason, 30 test specimens of a 50 vol%-mixture have been produced in two batches. The results of the compressive strength tests were then statistically evaluated. The underlying statistical distribution was determined by the Anderson-Darling-Test. Subsequently the 5 % fractile values of the mixtures, which represent the characteristic concrete compressive strength, were determined.

PH-dependent Release Matrix Oral Formulation of Prussian Blue to Improve its Efficacy as an Internal Decorporation Agent.

Prussian Blue (PB) is available as conventional release dosage form "Radiogardase" with effective daily dose of 3-10 g (very high). The target site is the duodenum, where it inhibits the enterohepatic circulation of Cs & Tl ions, enhancing their fecal excretion. To enhance efficacy, target release, reduce the dose and side effects, oral pH-dependent matrix formulation of PB based on in-situ gelation of sodium alginate along with calcium salts was formulated and evaluated. Different combinations of matrix granules were formulated and optimized. The optimized one was compressed using Polyvinylpyrrolidone K30 (Pvp K30) in different batches and optimized. Langmuir adsorption isotherm was used to assess in-vitro binding efficacy of formulation to thallium using atomic absorption spectroscopy. The proof of concept i.e., drug release in the duodenum was studied through pharmacoscintigraphy using radiolabeled formulation in rabbits. The optimized granules showed no drug release in an acidic medium for 2 h whereas complete empty of the basket in a basic medium within 30-60 minutes. The matrix tablet formulation with Pvp K30 (10% w/w) was optimized with desired hardness and optimum in-vitro release profile. The release data fitted to various linear kinetic models, Hixson-Crowell r2 (0.9906) best fit, confirmed the erosion-based release mechanism. The maximum binding capacity (MBC) was found significantly higher (89.60 mg Tl/g formulation) than that of PB API (65.90 mg Tl /g PB API). Pharmacoscintigraphic images confirmed intact formulation in the stomach up to 2h and burst release in intestine thereafter. The results exemplify oral pH-dependent PB matrix formulation which achieved desirable target release at the duodenum and in-vitro binding efficacy towards Tl ion was appreciable.

Hydrodynamically Balanced Capsule of Famotidine: An Improved Delivery via Gastroretentive Hydrogels

Objective: The aim of the present study was to increase the absolute bioavailability of famotidine, enhanced patient compliance in the treatment of peptic ulcer by increasing its gastric residence time and controlled local release of drug upto 12 hours. Materials and Methods: Hydrodynamically balanced capsules of famotidine were prepared, consisting of floating matrix granules, which formed hydrogels. Effects of different formulation variables namely hypromellose (HPMC 4000 cps, HPMC 5600 cps, HPMC 15000 cps), effervescent agent (potassium bicarbonate) and mixing time were studied. Optimization study included 23 full factorial design with t50% and t80% as the kinetic parameters (response variable). Matrix characterization included scanning electron microscopy. All prepared formulations were evaluated to various parameters such as micromeritics properties, % buoyancy and in vitro drug release studies. Results and Discussion: The optimized formulation (F4) remains buoyant for more than 12 hrs. The in-vitro drug release study indicated that increasing the viscosity of HPMC resulted in sustained drug release with long floating duration. SEM studies showed definite entrapment of the drug in the matrix and hydrogel formation. Results showed a pH independent but polymer viscosity dependent drug release profile. The release kinetics followed Higuchi model and mechanism of release was found to be non-Fickian diffusion. Conclusion: Famotidine-loaded hydrodynamically balanced capsules were successfully prepared and prove to be useful for prolonged gastric residence of the drug, better bioavailability, patient compliance and improve delivery for enhanced anti-ulcer activity.

Valorization of Rice Straw into Cellulose Microfibers for the Reinforcement of Thermoplastic Corn Starch Films

In the present study, agro-food waste derived rice straw (RS) was valorized into cellulose microfibers (CMFs) using a green process of combined ultrasound and heating treatments and were thereafter used to improve the physical properties of thermoplastic starch films (TPS). Mechanical defibrillation of the fibers gave rise to CMFs with cumulative frequencies of length and diameters below 200 and 5–15 µm, respectively. The resultant CMFs were successfully incorporated at, 1, 3, and 5 wt% into TPS by melt mixing and also starch was subjected to dry heating (DH) modification to yield TPS modified by dry heating (TPSDH). The resultant materials were finally shaped into films by thermo-compression and characterized. It was observed that both DH modification and fiber incorporation at 3 and 5 wt% loadings interfered with the starch gelatinization, leading to non-gelatinized starch granules in the biopolymer matrix. Thermo-compressed films prepared with both types of starches and reinforced with 3 wt% CMFs were more rigid (percentage increases of ~215% for TPS and ~207% for the TPSDH), more resistant to break (~100% for TPS and ~60% for TPSDH), but also less extensible (~53% for TPS and ~78% for TPSDH). The incorporation of CMFs into the TPS matrix at the highest contents also promoted a decrease in water vapor (~15%) and oxygen permeabilities (~30%). Finally, all the TPS composite films showed low changes in terms of optical properties and equilibrium moisture, being less soluble in water than the TPSDH films.

An Updated Overview on Mucoadhesive Buccal Drug Delivery System

Among the various routes of drug delivery, the oral route is an attractive site for the delivery of drugs. The main advantages of these formulations are: drug targeting, sustained release, increased permanence time in the buccal mucosa, increased bioavailability, and decreased potential adverse effects and maintains constant blood levels for extended period of time. The buccal cavity was found to be the most suitable and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery. Buccal mucosa has a tremendous availability, which leads to direct access to systemic circulation through the internal jugular vein bypasses the drug from hepatic first pass metabolism. The main disadvantage of this route is Limited absorption area- the total surface area of the membranes of the oral cavity available for drug absorption is 170 cm2 of which ~50 cm2 represents non-keratinized tissues, including buccal membrane, the barrier function of the skin changes from one site to the other and from one person to other person with age and large dose of drug are difficult to be administered. Melt granulation is emerging technique and this technique used to increase the dissolution rate of poorly water-soluble drugs. Tablet molding technique: Tablets produced by the molding technique are easier to scale up for industrial manufacture than lyophilisation technique. Hot melt extrusion of film method: Hot melt extrusion has been used for the manufacture of controlled release matrix tablets, pellets and granules, as well as oral disintegrating films.

Mitochondria in human acute myeloid leukemia cell lines have ultrastructural alterations linked to deregulation of their respiratory profiles

Mitochondria not only are essential for cell metabolism and energy supply but are also engaged in calcium homeostasis and reactive oxygen species generation and play a key role in apoptosis. As a consequence, functional mitochondrial disorders are involved in many human cancers including acute myeloid leukemia (AML). However, very few data are available on the deregulation of their number and/or shape in leukemic cells, despite the evident link between ultrastructure and function. In this context, we analyzed the ultrastructural mitochondrial parameters (number per cell, mitochondria area, number of cristae/mitochondria, cristal thickness) in five leukemia cell lines (HEL, HL60, K562, KG1, and OCI-AML3) together with the functional assay of their respiratory profile. First, we describe significant differences in basal respiration, maximal respiration, ATP production, and spare respiratory capacity between our cell lines, confirming the various respiratory profiles among leukemia subtypes. Second, we highlight that these variations are obviously associated with significant interleukemia heterogeneity of the number and/or shape of mitochondria. For instance, KG1, characterized by the smallest number of mitochondria together with reduced cristal diameter, had a particularly deficient respiratory profile. In comparison, the HEL and K562 cell lines, both with high respiratory profiles, harbored the largest number of mitochondria/cells with high cristal diameters. Moreover, we report that K562, carrying the ASXL1 mutation, presents significant mitochondria-endoplasmic reticulum deficiency reflected by decreases in the numbers of matrix granules and mitochondria-associated endoplasmic reticulum membrane (MAM) and mitochondrial-derived vesicle (MDV) precursors, which are implicated in the regulatory pathways of cell mortality via the processes of mitophagy and calcium homeostasis. Contrarily, HL60 carried high levels of matrix granules and MAMs and had a higher sensitivity to drugs targeting mitochondria (rotenone/antimycin). We confirm the implication of ASXL1 mutation in this mitochondria dysregulation through the study of transcript expression (from 415 patients with public data) involved in three mitochondrial pathways: (1) endoplasmic reticulum-mitochondria contacts (MAMs), (2) matrix granule homeostasis, and (3) MDV precursor production. Our study offers new and original data on mitochondria structural alterations linked to deregulation of respiration profiles in AMLs and some genetic characteristics, suggesting that modifications of mitochondrial shape and/or number in leukemic cells participate in chemoresistance and could be a targeted mechanism to regulate their proliferative potential.