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Abstract Cell adhesion to the extracellular matrix and its natural outcome of cell spreading, along with the maintenance of barrier activity, are essential behaviors of epithelial cells, including retinal pigment epithelium (RPE). Disruptions in these characteristics can result in severe vision-threatening diseases such as diabetic macular edema and age-related macular degeneration. However, the precise mechanisms underlying how RPE cells regulate their barrier integrity and cell spreading are not fully understood. This study aims to elucidate the relative importance of upper glycolytic components in governing these cellular behaviors of RPE cells. Electric Cell-Substrate Impedance Sensing (ECIS) technology was utilized to assess in real-time the effects of targeting various upper glycolytic enzymes on RPE barrier function and cell spreading by measuring cell resistance and capacitance, respectively. Specific inhibitors used included WZB117 for Glut1 inhibition, Lonidamine for Hexokinase inhibition, PFK158 for PFKFB3/PFK axis inhibition, and TDZD-8 for Aldolase inhibition. Additionally, the viability of RPE cells was evaluated using a lactate dehydrogenase (LDH) cytotoxicity assay. The most significant decrease in electrical resistance and increase in capacitance of RPE cells were observed due to dose-dependent inhibition of Glut1 using WZB117, as well as Aldolase inhibition with TDZD-8. LDH level analysis at 24–72 h post-treatment with WZB117 (1 and 10 μM) or TDZD-8 (1 μM) showed no significant difference compared to the control, indicating that the disruption of RPE functionality was not attributed to cell death. Lastly, inhibition of other upper glycolytic components, including PFKFB3/PFK with PFK158 or Hexokinase with Lonidamine, did not significantly affect RPE cell behavior. This study provides insights into the varied roles of upper glycolytic components in regulating the functionality of RPE cells. Specifically, it highlights the critical roles of Glut1 and Aldolase in preserving barrier integrity and promoting RPE cell adhesion and spreading. Such understanding will guide the development of safe interventions to treat RPE cell dysfunction in various retinal disorders.

Purpose: To report two cases of symptomatic posterior pole arterial occlusions in patients with hemoglobin SS disease. Observations: Two teenage patients with hemoglobin SS disease presented with visual distortions, and on dilated fundus examination and testing, they were found to have arterial occlusions involving the posterior pole. The patients were evaluated for stroke with head imaging and received exchange transfusion by hematology. Conclusions and Importance: This case series reports the unusual findings of arterial occlusions in the posterior pole resulting in areas of retinal whitening and ischemia in patients with HbSS. While sickle cell retinopathy is typically considered a peripheral retinal disease, these findings underscore the importance of vigilance when examining patients with sickle cell disease.

Background. To investigate Wnt/β-catenin signaling pathway expression and its regulation of type I collagen by TGF-β1 in scleral fibroblasts from form-deprivation myopia (FDM) guinea pig model. Methods. Wnt isoforms were examined using genome microarrays. Scleral fibroblasts from FDM group and self-control (SC) group were cultured. Wnt isoforms, β-catenin, TGF-β1, and type I collagen expression levels were examined in the two groups with or without DKK-1 or TGF-β1 neutralizing antibody. Results. For genome microarrays, the expression of Wnt3 in FDM group was significantly greater as confirmed in retinal and scleral tissue. The expression of Wnt3 and β-catenin significantly increased in FDM group and decreased significantly with DKK-1. TGF-β1 expression level decreased significantly in FDM group and increased significantly with DKK-1. Along with morphological misalignment inside and outside cells, the amount of type I collagen decreased in FDM group. Furthermore, type I collagen increased and became regular in DKK-1 intervention group, whereas it decreased and rearranged more disorder in TGF-β1 neutralizing antibody intervention group. Conclusions. The activation of Wnt3/β-catenin signaling pathway was demonstrated in primary scleral fibroblasts in FDM. This pathway further reduced the expression of type I collagen by TGF-β1, which ultimately played a role in scleral remodeling during myopia development.

Summary: Background: The real-world impact of bivalent vaccines for wild type (WA.1) and Omicron variant (BA.5) is largely unknown in immunocompromised patients with Multiple Myeloma (MM). We characterize the humoral and cellular immune responses in patients with MM before and after receiving the bivalent booster, including neutralizing assays to identify patterns associated with continuing vulnerability to current variants (XBB1.16, EG5) in the current post-pandemic era. Methods: We studied the humoral and cellular immune responses before and after bivalent booster immunization in 48 MM patients. Spike binding IgG antibody levels were measured by SARS-CoV-2 spike binding ELISA and neutralization capacity was assessed by a SARS-CoV-2 multi-cycle microneutralization assays to assess inhibition of live virus. We measured spike specific T-cell function using the QuantiFERON SARS-CoV-2 (Qiagen) assay as well as flow-cytometry based T-cell. In a subset of 38 patients, high-dimensional flow cytometry was performed to identify immune cell subsets associated with lack of humoral antibodies. Findings: We find that bivalent vaccination provides significant boost in protection to the omicron variant in our MM patients, in a treatment specific manner. MM patients remain vulnerable to newer variants with mutations in the spike portion. Anti-CD38 and anti-BCMA therapies affect the immune machinery needed to produce antibodies. Interpretation: Our study highlights varying immune responses observed in MM patients after receiving bivalent COVID-19 vaccination. Specifically, a subgroup of MM patients undergoing anti-CD38 and anti-BCMA therapy experience impairment in immune cells such DCs, B cells, NK cells and TFH cells, leading to an inability to generate adequate humoral and cellular responses to vaccination. Funding: National Cancer Institute (National Institutes of Health), National Institute of Allergy and Infectious Diseases (National Institutes of Health), NCI Serological Sciences Network for COVID-19 (SeroNet) and The Icahn School of Medicine at Mount Sinai.

The diabetic cornea exhibits pathological alterations, such as delayed epithelial wound healing and nerve regeneration. We investigated the role of semaphorin (SEMA) 3C in corneal wound healing and reinnervation in normal and diabetic B6 mice. Wounding induced the expression of SEMA3A, SEMA3C, and their receptor neuropilin-2 (NRP2), but not NRP1, in normal corneal epithelial cells; this upregulation was suppressed for SEMA3C and NRP2 in diabetic corneas. Injections of Sema3C-specific small interfering RNA and NRP2-neutralizing antibodies in wounded mice resulted in a decrease in the rate of wound healing and regenerating nerve fibers, whereas exogenous SEMA3C had opposing effects in diabetic corneas. NRP1 neutralization, on the other hand, decreased epithelial wound closure but increased sensory nerve regeneration in diabetic corneas, suggesting a detrimental role in nerve regeneration. Taken together, epithelium-expressed SEMA3C plays a role in corneal epithelial wound closure and sensory nerve regeneration. The hyperglycemia-suppressed SEMA3C/NRP2 signaling may contribute to the pathogenesis of diabetic neurotrophic keratopathy, and SEMA3C might be used as an adjunctive therapeutic for treating the disease. [ABSTRACT FROM AUTHOR]

Summary: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The proportion of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can be detected up to 3 months after symptom resolution. We investigated both seroconversion and PCR positivity in a large cohort of convalescent serum donors in the New York City (NY, USA) region. Methods: In this observational study, we ran an outreach programme in the New York City area. We recruited participants via the REDCap (Vanderbilt University, Nashville, TN, USA) online survey response. Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via ELISA for presence of anti-SARS-CoV-2 spike antibodies. One-way ANOVA and Fisher's exact test were used to measure the association of age, gender, symptom duration, and days from symptom onset and resolution with positive antibody results. Findings: Between March 26 and April 10, 2020, we measured SARS-CoV-2 antibody titres in 1343 people. Of the 624 participants with confirmed SARS-CoV-2 infection who had serologies done after 4 weeks, all but three seroconverted to the SARS-CoV-2 spike protein, whereas 269 (37%) of 719 participants with suspected SARS-CoV-2 infection seroconverted. PCR positivity was detected up to 28 days from symptom resolution. Interpretation: Most patients with confirmed COVID-19 seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks after symptom resolution, but it is unclear whether this signal represents infectious virus. Analysis of our large cohort suggests that most patients with mild COVID-19 seroconvert 4 weeks after illness, and raises questions about the use of PCR to clear positive individuals. Funding: None.

In order to reveal the degradation process and deterioration mechanism of cement-based materials, this paper analyzes the effects of carbonic acid leaching on the mechanical strength of mortars, as well as relative mass loss, microstructure, and composition of various cement pastes. The results indicate that cement pastes containing less than 20 % fly ash have higher carbonic acid leaching resistance than cement pastes without fly ash. However, after carbonic acid leaching, the compressive strength of the samples with fly ash is lower than that of the cement pastes without fly ash. The leaching resistance is good for samples cured at an early age before leaching. Carbonic acid leaching proceeds from the paste surface to the interior. The incorporation of an appropriate amount of slag powder helps to increase the density of the paste. Due to the pozzolanic activity of fly ash at late-stage leaching, a mixture of fly ash (≤ 20 %) and slag powder (≤ 20 %) effectively improves carbonic acid leaching resistance. The products of early-stage leaching were mainly CaCO₃ and small amounts of SiO₂ and Fe₂O₃. The C-S-H phase at the paste surface suffered serious damage after long periods of leaching, and the main products of leaching were SiO₂ and Fe₂O₃.

With the outbreak of the COVID-19 epidemic, masks have become an important medical material widely concerned by society, which also affects investor sentiment and mask concept stock prices. This article focuses on the impact of investor attention on the rate of return of mask concept stocks. Through the establishment of a panel fixed effect model, it is found that during the epidemic, investor attention to masks has a significant positive impact on the rate of return on mask concept stocks. Then, this article takes the epidemic-related indicators as instrumental variables and uses a two-stage least squares method to carry out the endogenous test, which further verifies the above conclusions and finally puts forward reasonable suggestions.

Prion diseases are rare, progressive and fatal neurodegenerative diseases characterized by long incubation period and short clinical course. We present a rare case of Heidenhain variant of Creutzfeldt-Jakob disease, occurring in a 55-year-old lady presenting with dementia, cortical blindness, and myoclonic jerks. She succumbed to the disease within 8 weeks of onset of symptoms. MRI revealed hyperintense signals on T2WI and fluid attenuated inversion recovery (FLAIR) images in basal ganglia and fronto-temporal and parietal cortex, sparing thalamus, striate cortex and globus pallidum. Abundant abnormal prion protein deposits (PrP sc) were detected in caudate, putamen, thalamus, cingulate and striate cortex, in comparison to frontal and parietal cortex while no deposits were found in globus pallidum. MRI changes did not correlate with degree of spongy change, gliosis or prion protein deposition. The cause for abnormal signal changes in MRI and FLAIR images remains unclear.

Abstract Introduction Malignant change in a leiomyoma or uterine fibroid is termed leiomyosarcoma. It arises from smooth muscle of the uterus and is a rare tumor that accounts for 2% to 5% of all uterine malignancies. Very few cases are reported in the literature. Our patient did not have any history of genital bleeding, which is the usual presentation in uterine sarcoma. We report an original case report of an unusual presentation of this rare tumor arising from the uterus. Case presentation A 40-year-old nulliparous woman of South Indian origin presented with a mass in her abdomen for one year with a rapid increase in size over the previous three months. Tumor marker CA-125 was raised, and a computed tomography scan showed a mass arising from the pelvis. An exploratory laparotomy was performed and the histopathology report confirmed the diagnosis of uterine leiomyosarcoma. Conclusion Because of their rarity, uterine sarcomas are not suitable for screening. Diagnosis is by histopathologic examination and surgery is the only treatment. The prognosis for women with uterine sarcoma primarily depends on the extent of disease at the time of diagnosis and the mitotic index.

Klebsiella pneumoniae is a member of the family Enterobacteriaceae, opportunistic pathogens that are among the eight most prevalent infectious agents in hospitals. The emergence of multidrug-resistant strains of K. pneumoniae has became a public health problem globally. To develop an effective antimicrobial agent, we isolated a bacteriophage, named JD001, from seawater and sequenced its genome. Comparative genome analysis of phage JD001 with other K. pneumoniae bacteriophages revealed that phage JD001 has little similarity to previously published K. pneumoniae phages KP15, KP32, KP34, and phiK02. Here we announce the complete genome sequence of JD001 and report major findings from the genomic analysis. [ABSTRACT FROM AUTHOR]

Biphasic floating minitablets of cefuroxime axetil were prepared by melt granulation technique using two different grades of gelucire namely 50/13 and 43/01 to maintain constant plasma drug concentration. Loading dose of cefuroxime axetil was formulated as immediate release (IR) minitablets by using hydrophilic grade of gelucire 50/13. Maintenance dose was formulated as floating sustained release (SR) minitablets by using hydrophobic grade of gelucire 43/01. The prepared IR and SR granules were subjected to micromeritic studies and scanning electron microscopy. Fourier transform infrared spectroscopy (FT-IR) study revealed that drug and selected carriers were compatible. In vitro dissolution study of optimized IR minitablets showed more than 85% of loading dose dissolved within 30 min. Optimized SR minitablets showed zero lag time with floating duration more than 12 h. The drug release from SR minitablets was linear with square root of time with non-Fickian diffusion-controlled release. The optimized batch of minitablets was filled into 0 size hard gelatin capsule. In vitro dissolution study for capsule showed an immediate burst release followed by SR up to 12 h. There is no significant change in dissolution data after storage at 40 °C and 75% RH for three months. Microbiological assay of dissolution samples of optimized minitablets filled in capsules showed proportionate increase in inhibition of growth against Escherichia coli up to 12 h samples. In vivo bioavailability study in albino rabbits showed three times improvement in oral bioavailability.

The objective of present research work was to design and characterize the venlafaxine HCl-loaded sodium alginate-based mucoadhesive microcapsules by ionic gelation technique using HPMC K100M as mucoadhesive polymer. The Placket-Burman Design was applied for preliminary screening of the formulations and systematic optimization by using Box-Behnken Design. The prepared microcapsules were characterized for drug content, entrapment efficiency, micromeritic properties, particle size, swelling index, mucoadhesive strength, in vitro drug release and in vivo antidepressant activity. FTIR and differential scanning calorimetry studies showed no incompatibility. Surface morphology studies revealed spherical nature of the prepared microcapsules. In vitro drug release studies revealed sustained release by diffusion mechanism. Further, the microcapsules were effective in reducing the depression induced by forced swimming test in Sprague-Dawley rats compared to the pure drug. The microcapsules were found to be stable under accelerated stability conditions, which suggest them as better alternative delivery systems for enhanced therapeutic efficacy of antidepressant drug, venlafaxine HCl.

The work was aim to design and characterize the sustained release mucoadhesive microspheres of Tolterodine tartrate prepared by non-aqueous solvent evaporation technique using ethyl cellulose based selected mucoadhesive polymers. Selected microspheres formulations of were found to be discrete, spherical and free flowing from the preliminary formulations. The microspheres exhibit good mucoadhesive property in in-vitro wash off test and showed high drug entrapment efficiency. Tolterodine tartrate release from these microspheres was slowed, extended and depended on the concentration of ethyl cellulose and type of mucoadhesive polymer used. In vitro drug release studies suggested that formulation F6c showed consistent drug release for up to 24 h time period. Among all the formulations, F6c containing ethyl cellulose with chitosan showed the reproducible results with best mucoadhesive profile and good surface morphology. The correlation value (r(2)) indicated that the drug release followed Higuchi model. Analysis of variance (ANOVA) showed significant difference in the release of drug from all formulations at P < 0.05 level. Accelerated stability study of optimized formulation (F6c) up to 3 month showed there was no change in drug content and release characteristics during storage.

Osmotic drug delivery system utilizes the principles of osmotic pressure for the controlled delivery of active pharmaceutical ingredient at a predetermined zero order rate. An appropriately designed osmotic drug delivery is not influenced by different physiologic factors but affected by pharmaceutical factors, which play a pivotal role in modulating the release of drug. The present review critically discussed about the factors affecting drug release from the delivery system such as solubility, osmotic pressure, size of delivery orifice and membrane characteristics. The major arena of this review is to highlight about the different types of osmotic drug delivery systems such as implantable, single chamber, multi chamber osmotic pumps and several specialized type of osmotic pumps. Apart from that this system is a versatile technology useful for delivery of drugs with varying solubility. The additional properties of this delivery system can also exhibit pulsatile release, burst release and colon targeting of drug. Because of its versatility, this above system seems to have promising approach which can result in improved safety profile, stable drug concentrations, uniform drug effects and dosing frequency. Current review also briefly discussed about the patents related to delivery of drugs by the principle osmotic pressure.

The objectives of present work was to design and characterize the rabeprazole sodium loaded microcapsules prepared by solvent evaporation technique using ethyl cellulose (EC) based various mucoadhesive polymer, followed by a triple coating with Eudragit L100. The Box-behnken design (BBD) was applied for optimization of formulations containing EC, HPMCK100M and Eudragit L100 as factors for selected responses like entrapment efficiency, mucoadhesive property and drug release in 24 h. The prepared microcapsules were characterized for particle size, drug content, swelling index, mucoadhesive strength, and in vivo antiulcer activity. FT-IR studies revealed that there was no drug-polymer interaction. SEM studies revealed that microcapsules were non-aggregated, spherical shape and smooth appearance. In vitro drug release data from microcapsules was fitted to different kinetic models to explain release profiles. The correlation coefficient value (r(2)) indicated that the drug release followed Higuchi model. Analysis of variance (ANOVA) showed significant difference in the release of drug from all formulations at p < 0.05 level. Accelerated stability study of optimized formulation (F4) upto 6 months showed there was no change in drug content and release characteristics during storage. In vivo antiulcer activity showed that the optimized microcapsules were able to protect rat stomach against ulcer formation vis-à-vis aqueous solution of the drug showed only negligible and minimum effect.

Proteins and peptides are the building blocks of human body and act as the arsenal to combat against the invading pathogenic organisms for treatment and management of diseases. Majority of such biomacromolecules are synthesized by the human body itself. However, entry of disease causing pathogens causes misleading in the synthesis of desired proteins for antibody formation. In such alarming situations, the delivery of requisite protein and peptide from external source helps in augmenting the body's immunity. The major drawbacks underlying poor biopharmaceutical performance of high molecular weight protein and peptide drugs are due to poor oral absorption, formulation stability, degradation in the gastric milieu, susceptible to presystemic metabolism. Numerous literature recounts the application of myriad drug delivery strategies for the effective delivery of protein and peptides viz. parentral, oral, transdermal, nasal, pulmonary, rectal, buccal and ocular drug delivery systems. There are many reviews on various delivery strategies for protein and peptide pharmaceuticals, but the present review article provides a bird's eye view on various novel drug delivery systems used for enhanced delivery of protein and peptide pharmaceuticals in the light of patent literature. Apart from this, the present manuscript endeavor provides idea on possible causes and major degradation pathways responsible for poor stability of protein and peptide drugs along with recent market instances on them utilizing novel drug delivery systems.

The current work aims to prepare the solid self-nanoemulsifying granules (SSNEGs) of ondansetron hydrochloride (ONH) to enhance its oral bioavailability by improving its aqueous solubility and facilitating its absorption though lymphatic pathways. Preformulation studies including screening of excipients for solubility and pseudoternary phase diagrams suggested the suitability of Capmul MCM as lipid, Labrasol as surfactant, and Tween 20 as cosurfactant for preparation of self-emulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the phase diagrams and subjected to thermodynamic stability studies and dispersibility tests. The prepared liquid SNEDDS formulations were characterized for viscosity, refractive index, droplet size and zeta potential. The TEM study confirmed the formation of nanoemulsion following dilution of liquid SNEDDS. The optimized liquid SNEDDS were transformed into free flowing granules by adsorption on the porous carriers like Sylysia (350, 550, and 730) and Neusilin™ US2. Solid state characterization employing the FTIR, DSC and powder XRD studies indicated lack of any significant interaction of drug with the lipidic and emulsifying excipients, and porous carriers. In vitro drug release studies indicated faster solubilization of the drug by optimized SSNEGs (over 80% within 30 min) vis-à-vis the pure drug (only 35% within 30 min). In vivo pharmacokinetic studies in Wistar rats observed significant increase in C(max) (3.01-fold) and AUC (5.34-fold) using SSNEGs compared to pure drug, whereas no significant difference (p>0.1) was observed with the liquid SNEDDS. Thus, the present studies ratify the bioavailability enhancement potential of SSNEGs of ONH prepared using porous carriers., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A combination of fusion and surface adsorption techniques was used to enhance the dissolution rate of cefuroxime axetil. Solid dispersions of cefuroxime axetil were prepared by two methods, namely fusion method using poloxamer 188 alone and combination of poloxamer 188 and Neusilin US2 by fusion and surface adsorption method. Solid dispersions were evaluated for solubility, phase solubility, flowability, compressibility, Kawakita analysis, Fourier transform-infrared spectra, differential scanning calorimetry, powder X-ray diffraction study, in vitro drug release, and stability study. Solubility studies showed 12- and 14-fold increase in solubility for solid dispersions by fusion method, and fusion and surface adsorption method, respectively. Phase solubility studies showed negative ΔG (0) tr values for poloxamer 188 at various concentrations (0, 0.25, 0.5, 0.75 and 1%) indicating spontaneous nature of solubilisation. Fourier transform-infrared spectra and differential scanning calorimetry spectra showed that drug and excipients are compatible with each other. Powder X-ray diffraction study studies indicated that presence of Neusilin US2 is less likely to promote the reversion of the amorphous cefuroxime axetil to crystalline state. in vitro dissolution studies, T50% and mean dissolution time have shown better dissolution rate for solid dispersions by fusion and surface adsorption method. Cefuroxime axetil release at 15 min (Q15) and DE15 exhibited 23- and 20-fold improvement in dissolution rate. The optimized solid dispersion formulation was stable for 6 months of stability study as per ICH guidelines. The stability was ascertained from drug content, in vitro dissolution, Fourier transform-infrared spectra and differential scanning calorimetry study. Hence, this combined approach of fusion and surface adsorption can be used successfully to improve the dissolution rate of poorly soluble biopharmaceutical classification system class II drug cefuroxime axetil.

Pharmaceutical research and inventions are increasingly developed for the design of an ideal dosage regimen in drug therapy of many diseases, which attains therapeutic concentration of drug in plasma and maintains it constant for the entire duration of treatment and also minimizes the side effects. Recent trends in pharmaceutical technology indicated that mucoadhesive micro particle and modified alginate beads as drug delivery system especially suitable for achieving delivery of drug in a predetermined rate locally or systemically for a prolonged period of time. The release of drug from microparticle depends on a variety of factors including carrier used to form the micro particle and amount of drug contained in them. The main aim of the present review is to explain the various theories, mechanisms, advanced mucoadhesive polymers, various delivery approaches, methodologies for developing a mucoadhesive micro-particle and modified alginate beads formulation, in vitro, ex vivo and in vivo characterization. Apart from this, an innovative test method that is biacore is highlighted in this review to measure the mucoadhesive strength. This review is also briefly explained about the updated patenting system for the development of micro-particle and modified alginate beads as drug delivery system.

Transdermal route has been recognized as a promising drug delivery system for systemic delivery of drugs and provides the advantage of avoidance of first-pass effect, ease of use, better patient compliance, maintaining constant blood level for longer period of time and decrease side effects. The major pitfalls of this route lie with difficulty in permeation of drugs through the skin. Several literatures have been published for enhancing the permeation of drugs by chemical approaches. However the present review highlighted about the advanced physical techniques used for enhancing delivery of drugs such as structure-based, electrically based, velocity based and several other miscellaneous physical techniques for enhancing the permeation of drugs. In addition to these, the present review also gives an exhaustive account on clinical data about these techniques and regulatory considerations for new drugs as well as generic product approval in transdermal drug delivery.

Hydroxy propyl methyl cellulose (HPMC) 5cPs, an aqueous soluble polymer was employed for coating diclofenac sodium (DFS) tablets 25 mg for protecting the integrity of the drug yet rendering the drug to release at a faster rate on contact with the gastric environment. Proper optimization for the aqueous based film coating formulation was undertaken primarily employing plasticizers like polyethylene glycol (PEG) 400 and propylene glycol (PG). The defect free selected formulations were further subjected for studying the effects of surfactants like sodium lauryl sulphate (SLS) and Tween-80 along with the plasticizers. The quality of the aqueous film coats or the plasticizer efficiency in case of PEG-400 is in the order 1.5 > 0.5 > 1.0% and for PG 1 > 4 > 3% which can be stated on the basis of less incidence of major coat defects like chipping, cracking, orange peel, roughness, blistering, blooming, picking. The quality of aqueous film coat or the surfactant efficiency in case of SLS + PEG-400 is in the order 0.3 < 0.5 < 0.1% and SLS + PG is in the order 0.5 < 0.1 < 0.3%. In case of Tween-80 + PEG-400 the order is 0.3 < 0.5 < 0.1% and Tween-80 + PG is in the order 0.3 < 0.1 < 0.5%. Elegant film formation can be stated from fewer incidences of coat defects. The obtained coated tablets eventually satisfied all the normal physical parameters like thickness, weights, and weight gain, drug content, crushing strength, percent friability, disintegration time, dissolution profile and possible drug-polymer interactions. ANOVA was undertaken followed by Dunnet multiple comparison for the dissolution profile considering uncoated as the standard. The difference was considered significant at p ⩽ 0.01.

Buccoadhesive tablets of carvedilol were prepared using HPMC K4M, HPMC K15M and Carbopol 934 as mucoadhesive polymers. Fifteen formulations were developed with varying concentrations of polymers. Formulations of the BC or BD series were composed of HPMC K4M or HPMC K15M in ratios of 1:1 to 1:5 whereas in the BE series Carbopol 934 was used (1:0.25 to 1:1.50). The formulations were tested for in vitro drug release, in vitro bioadhesion, moisture absorption and in vitro drug permeation through porcine buccal mucosa. Formulation BC3 showed maximum release of the drug (88.7 +/- 0.4%) with the Higuchi model release profile and permeated 21.5 +/- 2.9% of the drug (flux 8.35 +/- 0.291 microg h(-1)cm(-2)) permeation coefficient 1.34 +/- 0.05 cm h(-1)) through porcine buccal membrane. BC3 formulation showed 1.62 +/- 0.15 N of peak detachment force and 0.24 +/- 0.11 mJ of work of adhesion. FTIR results showed no evidence of interaction between the drug and polymers. XRD study revealed that the drug is in crystalline form in the polymer matrix. The results indicate that suitable bioadhesive buccal tablets with desired permeability could be prepared.

Solid dispersions of celecoxib with beta-cyclodextrins were prepared by physical mixing, slugging and kneading methods at 1:1 and 1:2 molar ratios and characterized by differential scanning calorimetry. Celecoxib suspensions were formulated employing its solid dispersions with sodium carboxymethylcellulose as the suspending agent. Stability studies were conducted by subjecting all the suspensions to freeze-thaw cycling. The suspensions were evaluated for particle size, sedimentation volume, viscosity, redispersibility and dissolution rate initially and after stability testing. Celecoxib suspensions formulated employing its solid dispersions exhibited good physical stability and gave higher dissolution rates than those formulated with celecoxib alone. The suspension prepared from solid dispersions (1:2) by the kneading method gave the highest improvement in dissolution rate and efficiency. Celecoxib in the inclusion complex with beta-cyclodextrin produced suspensions of better physical stability and dissolution rate.

Over the years, controlled drug delivery as well as site-specific delivery have made considerable advances. One area that contributed significantly to this progress is the rapidly developing field of colloidal drug delivery systems. Nanoparticles, one of the colloidal drug delivery systems, may enable new possibilities for therapy that presently have not been investigated. Recent advances in nanoparticle research are discussed here. The present review highlights new and upcoming developments such as nanosuspensions and solid lipid nanoparticles.