Microbial bionic nano-aromatic drugs for prevention of depression induced by chronic stress.

Depression is a mood disorder mainly clinically characterized by significant and persistent low spirits. Chronic stress is the leading cause of depression. However, traditional medicine has severe side effects in treating depression, ineffective treatment, and easy recurrence. Therefore, it is of great significance to prevent depression in the environment of chronic stress. In this study, aromatherapy was used for the prevention of depression. To solve the defects of intense volatility and inconvenience in using essential oils, we designed bionic nano-aromatic drugs and adhered them to the wallpaper. Inspired by the moldy wallpaper, we successively prepared the morphology-bionic nano-aromatic drugs, the function-bionic nano-aromatic drugs, and the bionic plus nano-aromatic drugs by referring to the morphology of microorganisms and substances in bacterial biofilms. Bionic nano-aromatic drugs remarkably promoted their adhesion on wallpaper. Molecular dynamics simulation explored its molecular mechanism. The essential oils, which were slowly released from the bionic nano-aromatic drugs, showed excellent biosecurity and depression prevention. These sustainedly released essential oils could significantly increase monoamine neurotransmitters in the brain under a chronic stress environment and had excellent neuroprotection. Besides, the bionic nano-aromatic drugs with simple preparation process and low cost had excellent application potential.

Development, optimization and characterization of cisplatin loaded cubosomes for human lung carcinoma.

OBJECTIVES: This study aimed to develop, optimize and evaluate glyceryl monooleate (GMO) based cubosomes as a drug delivery system containing cisplatin for treatment of human lung carcinoma. SIGNIFICANCE: The significance of this research was to successfully incorporate slightly water soluble and potent anticancer drug (cisplatin) into cubosomes, which provide slow and sustained release of drug for longer period of time. METHODS: The delivery system was developed through top-down approach by melting GMO and poloxamer 407 (P407) at 70 °C and then drop-wise addition of warm deionized water (70 °C) containing cisplatin. The formulation then exposed to probe sonicator for about 2 min. A randomized regular two level full factorial design with help of Design Expert was used for optimization of blank cubosomal formulations. Cisplatin loaded cubosomes were then subjected to physico-chemical characterization. RESULTS: The characterization of the formulation revealed that it had a sufficient surface charge of -9.56 ± 1.33 mV, 168.25 ± 5.73 nm particle size, and 60.64 ± 0.11% encapsulation efficiency. The in vitro release of cisplatin from the cubosomes at pH 7.4 was observed to be sustained, with 94.5% of the drug being released in 30 h. In contrast, 99% of cisplatin was released from the drug solution in just 1.5 h. In vitro cytotoxicity assay was conducted on the human lung carcinoma NCI-H226 cell line, the cytotoxicity of cisplatin-loaded cubosomes was relative to that of pure cisplatin solution, while blank (without cisplatin) cubosomes were nontoxic. CONCLUSIONS: The obtained results demonstrated the successful development of cubosomes for sustained delivery of cisplatin.

Cubosomes were prepared, optimized, and evaluated for cisplatin delivery.A randomized regular two level full factorial design was constructed to optimize blank cubosomes.Blank cubosomes consisted of GMO as the lipid and P407 as an emulsifying agent.In vitro release studies demonstrated sustained release of cisplatin from cubosomes at pH 7.4.Cytotoxicity assay on human lung carcinoma cell line NCI-H226 showed similar cytotoxicity between cisplatin-loaded cubosomes and pure cisplatin solution while blank cubosomes exhibited no toxicity.

A Water-Soluble Chitosan Derivative for the Release of Bioactive Deferoxamine.

Deferoxamine (DFO) is a water-soluble iron chelator used pharmacologically for the management of patients with transfusional iron overload. However, DFO is not cell-permeable and has a short plasma half-life, which necessitates lengthy parenteral administration with an infusion pump. We previously reported the synthesis of chitosan (CS) nanoparticles for sustained slow release of DFO. In the present study, we developed solid dispersions and nanoparticles of a carboxymethyl water-soluble chitosan derivative (CMCS) for improved DFO encapsulation and release. CS dispersions and nanoparticles with DFO have been prepared by ironical gelation using sodium triphosphate (TPP) and were examined for comparison purposes. The successful presence of DFO in CMCS polymeric dispersions and nanoparticles was confirmed through FTIR measurements. Furthermore, the formation of CMCS nanoparticles led to inclusion of DFO in an amorphous state, while dispersion of DFO in the polymeric matrix led to a decrease in its crystallinity according to X-ray diffraction (XRD) and differential scanning calorimetry (DSC) results. An in vitro release assay indicated sustained release of DFO from CS and CMCS nanoparticles over 48 h and 24 h, respectively. Application of CMCS-DFO dispersions to murine RAW 264.7 macrophages or human HeLa cervical carcinoma cells triggered cellular responses to iron deficiency. These were exemplified in the induction of the mRNA encoding transferrin receptor 1, the major iron uptake protein, and the suppression of ferritin, the iron storage protein. Our data indicate that CMCS-DFO nanoparticles release bioactive DFO that causes effective iron chelation in cultured cells.

In vitro and in vivo studies of micro-depots using tailored microemulsion for sustained local anaesthesia.

In clinical practice, lidocaine is used as local anesthetic for the management of post-operative pain. The commercial formulation including gels, injections and ointments showed short duration of action (1 to 2 h). In this paper, the efforts have being made to develop tailored lidocaine-microemulsion (o/w), which on penetration in the skin layer cause micro-depots formation due to destabilization of the microemulsion system. To identify the microemulsion region, pseudo ternary diagrams were constructed using Capmul MCM as oil, Pluronic F68 as tri-block surfactant, polyethylene glycol 200 as co-surfactant at 1:4 and 1:6 ratios (S:Co-S). The selected 5%w/v lidocaine loaded microemulsion [Ld-ME-2(1:4)] was stable in thermodynamic test and during shelf life period (3 months). In ex vivo permeability study, the lidocaine release from Ld-ME-2(1:4) microemulsion was sustained in comparison to the marketed lidocaine ointment. The skin irritation study confirmed the safety of lidocaine loaded microemulsion. Tail flick test showed improved and sustain local anaesthetic effect in comparison to the market ointment. The improved efficacy of microemulsion system, was due to high penetration in the skin layer due to local precipitation of lidocaine from microemulsion. The findings suggest that the tailored microemulsion could be a potential strategy to prolong the local anaesthesia.

Novel nanoformulation to mitigate co-effects of drugs of abuse and HIV-1 infection: towards the treatment of NeuroAIDS.

Drug abuse (e.g., methamphetamine-Meth or cocaine-Coc) is one of the major risk factors for becoming infected with HIV-1, and studies show that in combination, drug abuse and HIV-1 lead to significantly greater damage to CNS. To overcome these issues, we have developed a novel nanoformulation (NF) for drug-abusing population infected with HIV-1. In this work, a novel approach was developed for the co-encapsulation of Nelfinavir (Nel) and Rimcazole (Rico) using layer-by-layer (LbL) assembled magnetic nanoformulation for the cure of neuroAIDS. Developed NF was evaluated for blood-brain barrier (BBB) transmigration, cell uptake, cytotoxicity and efficacy (p24 assay) in HIV-1 infected primary astrocyte (HA) in presence or absence of Coc and Meth. Developed magnetic nanoformulation (NF) fabricated using the LbL approach exhibited higher amounts of drug loading (Nel and Rico) with 100% release of both the therapeutic agents in a sustained manner for 8 days. NF efficacy studies indicated a dose-dependent decrease in p24 levels in HIV-1-infected HA (~55%) compared to Coc + Meth treated (~50%). The results showed that Rico significantly subdued the effect of drugs of abuse on HIV infectivity. NF successfully transmigrated (38.8 ± 6.5%) across in vitro BBB model on the application of an external magnetic field and showed >90% of cell viability with efficient cell uptake. In conclusion, our proof of concept study revealed that sustained and concurrent release of sigma σ1 antagonist and anti-HIV drug from the developed novel sustained release NF can overcome the exacerbated effects of drugs of abuse in HIV infection and may solve the issue of medication adherence in the drug-abusing HIV-1 infected population.

The recombinant BMP-2 loaded silk fibroin microspheres improved the bone phenotype of mild osteogenesis imperfecta mice.

Osteogenesis imperfecta (OI) is an inherited congenital disorder, characterized primarily by decreased bone mass and increased bone fragility. Bone morphogenetic protein-2 (BMP-2) is a potent cytokine capable of stimulating bone formation, however, its rapid degradation and unanticipated in vivo effects restrict its application. The sustained release characteristic of silk fibroin (SF) microspheres may potentially address the aforementioned challenges, nevertheless they have not previously been tested in OI treatment. In the current investigation, recombinant BMP-2 (rBMP-2) loaded SF (rBMP-2/SF) microspheres-based release carriers were prepared by physical adsorption. The SF microparticles were characterized by scanning electron microscopy (SEM) and were investigated for their cytotoxicity behavior as well as the release profile of rBMP-2. The rBMP-2/SF microspheres were administered via femoral intramedullary injection to two genotypes of OI-modeled mice daily for two weeks. The femoral microstructure and histological performance of OI mice were evaluated 2 weeks later. The findings suggested that rBMP-2/SF spheres with a rough surface and excellent cytocompatibility demonstrated an initial rapid release within the first three days (22.15 ± 2.88% of the loaded factor), followed by a transition to a slower and more consistent release rate, that persisted until the 15th day in an in vitro setting. The factor released from rBMP-2/SF particles exhibited favorable osteoinductive activity. Infusion of rBMP-2/SF microspheres, as opposed to blank SF spheres or rBMP-2 monotherapy, resulted in a noteworthy enhancement of femoral microstructure and promoted bone formation in OI-modeled mice. This research may offer a new therapeutic approach and insight into the management of OI. However, further investigation is required to determine the systematic safety and efficacy of rBMP-2/SF microspheres therapy for OI.

Development of sustained release antipsychotic tablets using novel polysaccharide isolated from Delonix regia seeds and its pharmacokinetic studies.

A natural polysaccharide was isolated from the seeds of Delonix regia. The isolated polysaccharide could maintain aqueous equilibrium between the dosage form and the surrounding medium due to its massive competence of water absorption (80.72%) and swelling index (266.7%). The Scanning Electron Micrograph of a polysaccharide exhibits rough surface with pores and crevices, hence, the drug release will be retarded because of the drug particles entrapment in the pores and crevices. Further, the surface tension of polysaccharide is higher than that of water, which may facilitate sustained release of drugs from dosage forms. An antipsychotic drug, quetiapine fumarate has a short half-life of 6 h and administered multiple times per day. Hence the quetiapine fumarate oral sustained release tablets were formulated using this polysaccharide in the concentration of 5-30% to avoid the side effects and increase patient compliance. Dissolution of the developed tablets with 25% polysaccharide content showed a better release profile than the other batches (5-20%) at the end of 12 h. The strong matrix complex has low solubility in water, it does not dissolve rapidly and the drug continues to diffuse through the gel layer at a consistent rate. Drug release from the matrix tablets follows matrix type except F-4 and F-5 which follow first order and Hix.crow type. The bioavailability study was carried out using healthy male New Zealand white rabbits that show the AUC(0-inf) value for developed SR tablets is 1.44 times higher than the reference thus, indicating more efficient and sustained drug delivery capable of maintaining plasma drug levels better.

Development and Characterization of Hygroscopicity-Controlled Sustain Release Formulation of Divalproex Sodium.

Objectives: Divalproex sodium (DS), being a hygroscopic drug, requires low humidity during product manufacturing. This study aims to develop a hygroscopicity controlled sustained release formulation of DS that can be manufactured in relatively high humid conditions in facilities lacking dehumidifiers. Materials and Methods: This study focuses on the role of polyethylene glycol (PEG-8000) and hydroxypropyl methylcellulose (HPMC K100M) as polymers of choice to control hygroscopicity and retard release of DS using solid dispersion technique. In this study, homogeneous solid dispersions containing various ratios of PEG-8000, HPMC K100M, and DS were obtained via melt granulation technique. Fifteen different solid dispersions were prepared based on Box-Behnken experimental design created in MiniTab software. The obtained solid dispersions were separately broken down into granules and their hygroscopic properties were determined via moisture uptake studies. Granular solid dispersions were then compressed into tablets and their sustained release dissolution profiles were studied as per the United States Pharmacopoeia (USP) monograph of DS extended-release tablets. Dissolution profiles of all fifteen formulations were then analyzed in Box-Behnken experimental design under MiniTab software to determine an optimized formulation having low hygroscopic properties as well as required multipoint drug release as per USP monograph. The final optimized formulation was prepared and subjected to moisture uptake study to determine its hygroscopicity, dissolution study to determine drug release kinetics and fourier transform infrared (FTIR) and differential scanning calorimetry (DSC) analysis to determine molecular interactions between drug and polymers. Result: Optimized final formulation yielded granular solid dispersion with 28% less hygroscopicity compared to DS and tablets with an excellent release profile in accordance with USP monograph. FTIR and DSC analysis did not show any significant interaction between DS and components of the solid dispersion. Conclusion: Optimized formulation from this study can be used to manufacture divalproex extended-release tablets inside facilities lacking dehumidifiers.

Lipid-based Nanocarriers Loaded with Taxanes for the Management of Breast Cancer: Promises and Challenges.

Breast cancer is the leading cause of deaths worldwide among women. Taxanes (most propitious class of diterpenes) have shown dynamic potentials in the treatment of early and metastatic breast cancer. However, challenges like poor bioavailability, low tissue-permeability, compromised aqueous solubility, and dose-dependent side-effects limit the clinical applications of these drugs. Henceforth, to overcome these challenges, various nanotechnology-based drug delivery systems are being explored for the delivery of taxanes in the management of breast cancer. One such promising nanocarrier category is lipid-based nanocarriers, which employ the meritorious features of a variety of lipids, both of natural and synthetic origin. It is also known that lipid uptake plays a significant role in breast cancer cells proliferation and tumor genesis. However, lipid-based nanocarriers could be a great choice to nanoencapsulate the poorly soluble and permeable taxanes for breast cancer management. These systems have an immense promise of bioavailability enhancement, spatial and temporal taxane delivery, improved efficacy, reduced dosing frequency, and even mild inhibition of the P-gp efflux mechanism. Apart from these promises, these carriers are not yet available for the benefit of the end-user. The present review will not only discuss the merits, progress, and promises of these systems but also ponder upon the various challenges faced by these carriers to reach the clinics for the benefit of the patients afflicted with breast cancer.

Superhydrophobic Surface for Enhancing the Bioavailability of Salbutamol Sulfate from Cross-Linked Microspheres: Formulation, Characterization, and in vivo Evaluation.

INTRODUCTION: The aim of the work was to formulate salbutamol sulfate (SB) microspheres by using superhydrophobic surface (SHS) under different processing factors for improving its encapsulation efficiency, controling its release rate, and hence enhancing its bioavailability. METHODS: Cross-linked microspheres of chitosan (CN) and carrageenan (KN) were made on a SHS under a glutaraldehyde-saturated atmosphere. The formulations were designed and optimized based on 42 factorial design. Percentage encapsulation efficiency (%EE), particle size, swelling ratio, and in vitro release rate were characterized, and the in vivo performance of optimized formula was investigated in beagle dogs. RESULTS: The results showed that the prepared microspheres have a high %EE (97.11±0.78%) for F13. The swelling ratio was 4.2 at the end of the 8 hours for the optimized formula, and the in vitro release rate was controlled for 12 hours. In vivo study verified that there was a 1.61-fold enhancement in SB bioavailability from optimized formula (F13) compared to market tablet. CONCLUSION: The study suggested that microspheres prepared from CN/KN crosslinking on an SHS using glutaraldehyde atmosphere is a promising technique that can encapsulate and sustain the release of water-soluble drugs such as SB in addition to improving its in vivo pharmacokinetic profile.

Fabrication and Evaluation of Spironolactone-Loaded Nanostructured Lipid Carries for Cardiac Tissue Regeneration.

BACKGROUND: Spironolactone (SP) is a lipophilic aldosterone receptor antagonist that few studies have reported its effect on cardiac remodeling. In addition, fewer researches have considered its influence on cardiomyocyte viability and potential benefits for myocardial tissue remodeling. METHOD: In this study, stearic acid (SA) (solid lipid) and oleic acid (OA) (liquid lipid) were utilized to produce nanostructured lipid carries (NLCs) (various ratios of SA to OA and water amount, F1: 80:20 [30 ml water], F2: 80:20 [60 ml water], F3: 70:30 [30 ml water], and F4: 70:30 [60 ml water]) containing SP and their particle size, polydispersity index, zeta potential, entrapment efficiency, and release profile were measured. The purpose of encapsulating SP in NLCs was to provide a sustain release system. Meanwhile, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay with different concentrations of SP-loaded NLCs (SP-NLCs) was conducted to evaluate the cytotoxicity of the NLCs on rat myocardium cells (H9C2). RESULTS: Increase of oil content to 10 wt% reduced the particle size from 486 nm (F1) to 205 nm (F2). Zeta potential of the samples at around -10 mV indicated their agglomeration tendency. After 48 h, SP-NLCs with the concentrations of 5 and 25 µM showed significant improvement in cell viability while the same amount of free SP-induced cytotoxic effect on the cells. SP-NLCs with higher concentration (50 µM) depicted cytotoxic effect on H9C2 cells. CONCLUSION: It can be concluded that 25 µM SP-NLCs with sustain release profile had a beneficial effect on cardiomyocytes and can be used as a mean to improve cardiac tissue regeneration.

Mini-Tablets versus Nanoparticles for Controlling the Release of Amoxicillin: In vitro/In vivo Study.

INTRODUCTION: Controlling the drug release from the dosage form at a definite rate is the main challenge for a successful oral controlled-release drug delivery system. In this study, mini-tablets (MTs) and lipid/polymer nanoparticles (LPNs) of lipid polymer and chitosan in different ratios were designed to encapsulate and control the release time of Amoxicillin (AMX). METHODS: Physical characteristics and in vitro release profiles of both MT and LPN formulations were studied. Antimicrobial activity and oral pharmacokinetics of the optimum MT and LPN formulations in comparison to market tablet were studied in rats. RESULTS: All designed formulations of AMX as MTs and LPNs showed accepted characteristics. MT-6 (Compritol/Chitosan 1:1) showed the greatest retardation among all prepared minitablet preparations, releasing about 79.5% of AMX over 8 h. In contrast, LPN-11 (AMX: Cr 1:3/Chitosan 1 mg/mL) had the slowest drug release, revealing the sustained release of 80.9% within 8 h. The MIC of both optimized tablet formula (MT-6) and LPNs formula (LPN-11) was around two-fold lower than the control against H. pylori. The Cmax of MT-6 and LPN11 were non significantly different compared with the marketed AMX product. While the bioavailability experiment proved that the relative bioavailability of the AMX was 1.85 and 1.8 after the oral use of LPN11 and MT-6, respectively, compared to the market tablet. CONCLUSION: The results verified that both controlled-release mini-tablets and lipid/polymer nanoparticles can be used for sustaining the release and hence improve the bioavailability of amoxicillin.

Preparation and characterization of bear bile-loaded pH sensitive in-situ gel eye drops for ocular drug delivery.

OBJECTIVES: In this study, a stable bear bile-loaded pH sensitive in-situ eye drop gel was prepared for sustain delivery and enhanced therapeutic application. MATERIALS AND METHODS: Bear bile-loaded in-situ ocular gels with different Carbopol/Hydroxypropyl methylcellulose (HPMC) ratios were prepared and their stability was tested in PBS at a series of pH at 40 °C. The morphology was observed by SEM examination and rheology was observed by Rheometer equipped with a 60-mm cone-plate at apex angle of 1°. Gel erosion and release kinetics of Tauroursodeoxycholic acid (TUDCA) was determined by HPLC. While, the in vivo dwelling time was obtained after administering the fluorescent-loaded gel in ocular disease-free New Zealand rabbits. Finally, biocompatibility and toxicity was observed by irritation test and H&E staining of eye-ball tissues, respectively. RESULTS: The bear bile-loaded in-situ ocular gel showed excellent stability at different pH (pH 5.0, 5.5, 6.0, 6.5, 7.0 and 8.0) up to 5 days, and bear bile extract significantly attenuated the gelling ability of the in-situ gel. The viscosity of in-situ gels formulation was decreased with increase in shear rate (0.01 to 100 s-1), and morphological examination of freeze-dried preparation showed three-dimensional reticular structure at physiological pH. The in-situ ocular gel exhibited promising sustained drug release up to 160 min in vitro, and showed prolonged retention time up to 3-folds in vivo. Finally, the biocompability data confirmed that the formulation did not induce any toxic effects and was completely compatible with eye tissues. CONCLUSION: pH sensitive in-situ ocular gel provides new research opportunities to efficiently treat eye diseases.

Effect of Poly(vinyl alcohol) on Nanoencapsulation of Budesonide in Chitosan Nanoparticles via Ionic Gelation and Its Improved Bioavailability.

Chitosan (CS) is a polymer extensively used in drug delivery formulations mainly due to its biocompatibility and low toxicity. In the present study, chitosan was used for nanoencapsulation of a budesonide (BUD) drug via the well-established ionic gelation technique and a slight modification of it, using also poly(vinyl alcohol) (PVA) as a surfactant. Scanning electron microscopy (SEM) micrographs revealed that spherical nanoparticles were successfully prepared with average sizes range between 363 and 543 nm, as were measured by dynamic light scattering (DLS), while zeta potential verified their positive charged surface. X-ray diffraction (XRD) patterns revealed that BUD was encapsulated in crystalline state in nanoparticles but with a lower degree of crystallinity than the neat drug, which was also proven by differential scanning calorimetry (DSC) and melting peak measurements. This could be attributed to interactions that take place between BUD and CS, which were revealed by FTIR and by an extended computational study. An in vitro release study of budesonide showed a slight enhancement in the BUD dissolution profile, compared to the neat drug. However, drug release was substantially increased by introducing PVA during the nanoencapsulation procedure, which is attributed to the higher amorphization of BUD on these nanoparticles. The release curves were analyzed using a diffusion model that allows estimation of BUD diffusivity in the nanoparticles.

Curcumin ameliorates the targeted delivery of methotrexate intercalated montmorillonite clay to cancer cells.

Montmorillonite Clay (MMT) is aimed to develop as an orally administrable drug delivery vehicle with enhanced efficacy. Aiming to enhance the therapeutic index of methotrexate, curcumin is concomitantly used with methotrexate in the present study. Being folate antagonist in nature, methotrexate is internalized into cells by folate receptor (FR); which is over-expressed in certain human cancer cells such as cervical carcinoma cells (HeLa). Firstly, montmorillonite Clay (MMT) is organically modified (OMMT) with cetyl trimethyl ammonium bromide (CTAB) and used to intercalate curcumin and methotrexate separately, designated as OMMT-Cur and OMMT-MTX, respectively. XRD pattern demonstrated successful intercalation of therapeutics and an increase in clay interlayer distance facilitated by CTAB. The dissolution kinetics of methotrexate follows Higuchi model for both Simulated Gastric Fluid (SGF) and Simulated Intestinal Fluid (SIF), while the release kinetics for curcumin fitted into Higuchi model for SGF and Hixson-Crowell model for SIF, respectively. OMMT-MTX are able to discriminate FR-positive HeLa cells from FR-negative breast cancer cells (MCF7); irrespective of alike cellular phenotypes. Further, the pre-treatment of HeLa cells with curcumin improves its sensitivity towards methotrexate causing a greater killing of the Hela cells. Together, the results propose the concomitant use of curcumin and methotrexate for successfully targeting highly invasive FR-positive carcinomas by means of folate receptor using MMTs.

Trends on polymer- and lipid-based nanostructures for parenteral drug delivery to tumors.

PURPOSE: The dawn of the state-of-the-art methods of cancer treatments, nano-based delivery systems, has dispensed with the mainstream chemotherapy for being inadequate in yielding productive results and the numerous reported side effects. The popularity of this complementary approach in the course of the last two decades has been primarily attributed to its capacity to elevate the therapeutic index of anticancer drugs as well as removing the impassable delivery barriers in solid tumors with the minimal damage to the normal tissues. METHODS: The PubMed database was consulted to compile this review. RESULTS: A wide range of minuscule organic and inorganic nanomaterials, with dimensions not exceeding hundred nanometers, has led to hope for cancer therapy to flare-up once again due to possessing a number of exclusive traits for passive and active tumor targeting, some of which are EPR effect, high interstitial pressure of tumor, overexpressed receptors and angiogenesis. Although a limited number of liposomal and polymer-based therapeutic nanoparticles have gained applicability, a vast number of nanoparticles are still being trailed in order to be fully developed. CONCLUSIONS: This study provides an overview of the advantages/disadvantages of nanocarriers for cancer drug delivery.

Application of Metal-Organic Framework Nano-MIL-100(Fe) for Sustainable Release of Doxycycline and Tetracycline.

Nanostructures of MIL-100 were synthesized and used as a drug delivery platform for two members of the Tetracycline family. Doxycycline monohydrate (DOX) and Tetracycline hydrochloride (TC) were loaded separately on nano-MIL-100 (nanoparticles of drug@carrier were abbreviated as DOX@MIL-100 and TC@MIL-100). Characterizations were carried out using FT-IR, XRD, BET, DLS, and SEM. The FT-IR spectra revealed that the drugs were loaded into the framework of the carrier. The XRD patterns of DOX@MIL-100 and TC@MIL-100 indicated that no free DOX or TC were present. It could be concluded that the drugs are well dispersed into the pores of nano-MIL-100. The microporosity of the carrier was confirmed by BJH data. BET analysis showed a reduction in the free surface for both DOX@MIL-100 and TC@MIL-100. The release of TC and DOX was investigated, and it was revealed that MIL-100 mediated the drug solubility in water, which in turn resulted in a decrease in the release rate of TC (accelerating in DOX case) without lowering the total amount of released drug. After 48 h, 96 percent of the TC was sustain released, which is an unprecedented amount in comparison with other methods.

Gamma scintigraphic study of the hydrodynamically balanced matrix tablets of Metformin HCl in rabbits.

The purpose of this study is to evaluate the in vitro and in vivo performance of gastro-retentive matrix tablets having Metformin HCl as model drug and combination of natural polymers. A total of 16 formulations were prepared by a wet granulation method using xanthan, tamarind seed powder, tamarind kernel powder and salep as the gel-forming agents and sodium bicarbonate as a gas-forming agent. All the formulations were evaluated for compendial and non-compendial tests and in vitro study was carried out on a USP-II dissolution apparatus at a paddle speed of 50 rpm. MOX2 formulation, composed of salep and xanthan in the ratio of 4:1 with 96.9% release, was considered as the optimum formulation with more than 90% release in 12 hours and short floating lag time. In vivo study was carried out using gamma scintigraphy in New Zealand White rabbits, optimized formulation was incorporated with 10 mg of (153)Sm for labeling MOX2 formulation. The radioactive samarium oxide was used as the marker to trace transit of the tablets in the gastrointestinal tract. The in vivo data also supported retention of MOX2 formulation in the gastric region for 12 hours and were different from the control formulation without a gas and gel forming agent. It was concluded that the prepared floating gastro-retentive matrix tablets had a sustained-release effect in vitro and in vivo, gamma scintigraphy played an important role in locating the oral transit and the drug-release pattern.

Gamma scintigraphic evaluation of floating gastroretentive tablets of metformin HCl using a combination of three natural polymers in rabbits.

The present research was aimed at formulating a metformin HCl sustained-release formulation from a combination of polymers, using the wet granulation technique. A total of 16 formulations (F1-F16) were produced using different combinations of the gel-forming polymers: tamarind kernel powder, salep (palmate tubers of Orchis morio), and xanthan. Post-compression studies showed that there were no interactions between the active drug and the polymers. Results of in vitro drug-release studies indicated that the F10 formulation which contained 5 mg of tamarind kernel powder, 33.33 mg of xanthan, and 61.67 mg of salep could sustain a 95% release in 12 hours. The results also showed that F2 had a 55% similarity factor with the commercial formulation (C-ER), and the release kinetics were explained with zero order and Higuchi models. The in vivo study was performed in New Zealand White rabbits by gamma scintigraphy; the F10 formulation was radiolabeled using samarium (III) oxide ((153)Sm2O3) to trace transit of the tablets in the gastrointestinal tract. The in vivo data supported the retention of F10 formulation in the gastric region for 12 hours. In conclusion, the use of a combination of polymers in this study helped to develop an optimal gastroretentive drug-delivery system with improved bioavailability, swelling, and floating characteristics.

Formulation and development of pH-independent/dependent sustained release matrix tablets of ondansetron HCl by a continuous twin-screw melt granulation process.

The objective of the present study was to develop pH-independent/dependent sustained release (SR) tablets of ondansetron HCl dihydrate (OND), a selective 5-HT3 receptor antagonist that is used for prevention of nausea and vomiting caused by chemotherapy, radiotherapy and postoperative treatment. The challenge with the OND API is its pH-dependent solubility and relatively short elimination half-life. Therefore, investigations were made to solve these problems in the current study. Formulations were prepared using stearic acid as a binding agent via a melt granulation process in a twin-screw extruder. The micro-environmental pH of the tablet was manipulated by the addition of fumaric acid to enhance the solubility and release of OND from the tablet. The in vitro release study demonstrated sustained release for 24h with 90% of drug release in formulations using stearic acid in combination with ethyl cellulose, whereas 100% drug release in 8h for stearic acid-hydroxypropylcellulose matrices. The formulation release kinetics was correlated to the Higuchi diffusion model and a non-Fickian drug release mechanism. The results of the present study demonstrated for the first time the pH dependent release from hydrophilic-lipid matrices as well as pH independent release from hydrophobic-lipid matrices for OND SR tablets manufactured by means of a continuous melt granulation technique utilizing a twin-screw extruder.