Microbial Profile, Antimicrobial Susceptibility, and Prevalence of MDR/XDR Pathogens Causing Medical Device Associated Infections: A Single Center Study.

Background: There is a scarcity of studies evaluating the microbial profile, antimicrobial susceptibility, and prevalence of MDR/XDR pathogens causing medical device-associated infections (MDAIs). The present study was sought in this regard. Materials and methods: An ambispective-observational, site-specific, surveillance-based study was performed for a period of 2 years in the intensive care unit (ICU) and high dependency unit (HDU) (medicine/surgery) of a Tertiary-care University Hospital. Three commonly encountered MDAIs including central-line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), and ventilator-associated pneumonia (VAP), were targeted. Results and conclusion: Of the total 90 patients, 46 (51.1%) were admitted to the ICU (medicine/surgery), and the remaining 44 (48.8%) were admitted to the HDU (medicine/surgery). The median (P25-P75) age of the total patients was 55 (43.1-62.3) years. Male 61 (67.8%) preponderance was observed. Sixty-two of 90 (68.9%) were immunocompromised. A total of 104 pathogens causing MDAIs were isolated. Staphylococcus epidermidis (CoNS), and Staphylococcus capitis were commonly isolated multi-drug resistant (MDR) gram-positive pathogens causing MDAIs. Similarly, carba-resistant Klebsiella pneumoniae, Stenotrophomonas maltophilia, and carba-resistant Acinetobacter baumanni were commonly isolated MDR gram-negative pathogens causing MDAIs. Five of 9 (55.5%) K. pneumoniae and three of 9 (33.3%) S. maltophilia isolates were found to be extensively drug resistant. Among Candida, C. parapsilosis was the most prevalent fungal pathogen causing CLABSI and CAUTI in patients admitted to ICU/HDU. How to cite this article: Suryawanshi VR, Pawar A, Purandare B, Vijayvargiya N, Sancheti S, Philip S, et al. Microbial Profile, Antimicrobial Susceptibility, and Prevalence of MDR/XDR Pathogens Causing Medical Device Associated Infections: A Single Center Study. Indian J Crit Care Med 2024;28(2):152-164.

An Overview of Chemistry, Kinetics, Toxicity and Therapeutic Potential of Boldine in Neurological Disorders.

Boldine is an alkaloid obtained from the medicinal herb Peumus boldus (Mol.) (Chilean boldo tree; boldo) and belongs to the family Monimiaceae. It exhibits a wide range of pharmacological effects such as antioxidant, anticancer, hepatoprotective, neuroprotective, and anti-diabetic properties. There is a dearth of information regarding its pharmacokinetics and toxicity in addition to its potential pharmacological activity. Boldine belongs to the aporphine alkaloid class and possesses lipophilic properties which enable its efficient absorption and distribution throughout the body, including the central nervous system. It exhibits potent free radical scavenging activity, thereby reducing oxidative stress and preventing neuronal damage. Through a variety of neuroprotective mechanisms, including suppression of AChE and BuChE activity, blocking of connexin-43 hemichannels, pannexin 1 channel, reduction of NF-κß mediated interleukin release, and glutamate excitotoxicity which successfully reduces neuronal damage. These results point to its probable application in reducing neuroinflammation and oxidative stress in epilepsy, Alzheimer's disease (AD), and Parkinson's disease (PD). Moreover, its effects on serotonergic, dopaminergic, opioid, and cholinergic receptors were further investigated in order to determine its applicability for neurobehavioral dysfunctions. The article investigates the pharmacokinetics of boldine and reveals that it has a low oral bioavailability and a short half-life, requiring regular dosage to maintain therapeutic levels. The review studies boldine's potential therapeutic uses and mode of action while summarizing its neuroprotective benefits.  Given the favorable results for boldine as a potential neurotherapeutic drug in laboratory animals, more research is required. However, in order to optimise its therapeutic potential, it must be more bioavailable with fewer detrimental side effects.

Brain Targeted Curcumin Loaded Turmeric Oil Microemulsion Protects Against Trimethyltin Induced Neurodegeneration in Adult Zebrafish: A Pharmacokinetic and Pharmacodynamic Insight.

PURPOSE: Aromatic turmerone, a major constituent of turmeric oil, has been recently reported for proliferation of neural stem cell showing great potential for effective treatment in neurodegenerative disorders. However, its effect as oral brain targeted formulation for neuroprotection has not yet reported. The objective of the study was to investigate the pharmacokinetic of curcumin loaded turmeric oil microemulsion for brain targeting and probing the protective effect against trimethyltin induced neurodegeneration in adult zebrafish. METHODS: Initially, in vivo plasma and brain pharmacokinetics was performed to determine improvement in relative bioavailability in rats followed by biodistribution and histopathological evaluation. Furthermore, the neuroprotective effect of the formulation was assessed in trimethyltin induced neurodegeneration model using adult zebrafish by behavioral analysis and biochemical analysis. RESULTS: The in vivo plasma and brain pharmacokinetics showed 2-fold and 1.87-fold improvement respectively. Biodistribution study revealed significantly lower concentration in organs other than brain. Furthermore, curcumin microemulsion exhibited improved spatial memory by remembering the training and made correct choices after curcumin microemulsion treatment than other treatment groups. Histopathological evaluation confirmed neuroprotective effect on zebrafish brains. The biochemical analysis revealed reduced oxidative stress in curcumin microemulsion treated group. CONCLUSIONS: Overall results showed a great potential of curcumin microemulsion for brain targeting in the effective treatment of neurological ailments.

Investigation of dimyristoyl phosphatidyl glycerol and cholesterol based nanocochleates as a potential oral delivery carrier for methotrexate.

Methotrexate (MTX), a biopharmaceutical classification system-IV anticancer drug, exhibits low therapeutic efficacy. Moreover, its clinical applications were restricted due to its multidrug resistance (MDR) in cancer and its toxic effects. The present investigation was to fabricate 1, 2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium (DMPG-Na), (3ß)-cholest-5-en-3-ol (cholesterol) and calcium-based nanocochleates (NCs) as a potential oral delivery carrier for MTX to enhance its therapeutic efficacy with low toxicity. MTX-loaded NCs (MTX-NCs) was developed by the addition of calcium ion into preformed nanoliposomes (MTX-NLs) comprising MTX, DMPG-Na, with cholesterol and evaluated by in-vitro and in-vivo methods in comparison with MTX-NLs and pure MTX. Stable tubular rod structure of MTX-NCs possessing particle size, encapsulation efficiency and zeta potential of 374.1 ± 2.2 nm, 78.63 ± 2.12% and -71.2 mV, respectively were obtained from homogenous unilamellar, discrete and spherical structured MTX-NLs with a diameter and zeta potential of 363.3 ± 3.7 nm and -74.6 mV respectively. A thermal study revealed an amorphous state of MTX in MTX-NCs. Pharmacokinetics study in rats, MTX-NLs and MTX-NCs were showed controlled release with 5 and 6 fold improvements in oral bioavailability. Moreover, MTX-NCs showed low tissue distribution. These results collectively suggest that the developed system could be used to improve the therapeutic efficacy of MTX.

Case report on hypersensitivity to methotrexate infusion in a pediatric acute lymphoblastic leukaemia patient.

Methotrexate is extensively used in the treatment of various malignancies and autoimmune conditions. Methotrexate is associated with several toxicities, while hypersensitivity reactions to methotrexate are unusual, but have been reported in adult cancer patients. Hereby, we detail the case of a child with acute lymphoblastic leukaemia who developed a hypersensitivity reaction to high-dose methotrexate infusion (HDMTX) during the fourth cycle of HDMTX. The child was rechallenged with another brand of methotrexate; she started complaining of itching on trunk within 5 min of infusion. Few studies have reported that desensitization has been helpful in children with hypersensitivity reactions allowing the continuation of HDMTX. However, it was decided to omit parenteral methotrexate for this child. Cranial radiotherapy was given for CNS prophylaxis. In conclusion, unexpected hypersensitivity with methotrexate should be kept in mind during the treatment especially with high-dose infusion.

Investigation of 1,2-Dimyristoyl-sn-Glycero-3-Phosphoglycerol-Sodium (DMPG-Na) Lipid with Various Metal Cations in Nanocochleate Preformulation: Application for Andrographolide Oral Delivery in Cancer Therapy.

This study aimed at carrying out a preformulation investigation of nanocochleates (NCs) and develop andrographolide-loaded nanocochleates. Preformulation study comprised of exploring the effect of trivalent and divalent ions on transition temperature (TT) of lipid (DMPG-Na), on particle size (PS), entrapment efficacy (EE), zeta potential (ZP) of NCs, and effect of NCs on change in lipid solubility post-NC formation. Further, the andrographolide-loaded nanocochleates made with CaCl2 (ANDNCs) were characterized for ZP, PS, EE, X-ray powder diffraction (PXRD), differential scanning calorimetry (DSC), transition electron microscopy (TEM), in vitro release studies, in vitro anticancer potential on the cell line of human breast cancer (MCF-7), in vivo oral pharmacokinetic studies, and tissue distribution in female Wistar rats. Nanocochleates developed with CaCl2 had a significant reduction in PS (1.78-fold) and ZP (1.38-fold), and elevation of EE (1.17-fold) as compared to AlCl3 developed NCs. Trivalent ions demonstrated elevation of TT as compared to divalent ions. Spiral-shaped ANDNCs demonstrated ZP, PS, and EE of - 121.46 ± 15.12 mV, 360 ± 47 nm, and 68.12 ± 3.81% respectively. In vitro release study of ANDNCs showed a strong pH-dependent release profile due to hydrogen bonding between NCs and andrographolide (AND). Formulated ANDNCs demonstrated 26.99-fold decrease in IC50 value as compared to free AND. Additionally, the oral bioavailability of AND from ANDNCs improved by 1.81-fold as compared to free AND. Furthermore, ANDNCs showed minimum accumulation within the vital organs such as liver, kidney, and spleen. Briefly, the preformulation study laid a platform for better understanding the NCs and its components. Further, developed ANDNCs revealed superior physiochemical properties to be used as an alternative for a clinical setting.

Effect of USP Induction Ports, Glass Sampling Apparatus, and Inhaler Device Resistance on Aerodynamic Patterns of Fluticasone Propionate-Loaded Engineered Mannitol Microparticles.

The present investigation is to study the effect of two different induction ports (IP), i.e., USP IP and USP-modified IP equipped with andersen cascade impactor on in vitro aerodynamic performance along with the impact of USP-modified glass sampling apparatus on delivered dose uniformity of fluticasone propionate (FP) dry powder inhaler (DPI). FP DPI was fabricated by spray drying technique using engineered mannitol microparticles (EMP) with different force controlling agents, i.e., leucine and magnesium stearate. Additionally, commercially available two DPI inhaler devices namely Handihaler® and Breezhaler® were used to aerosolize the FP blends. Spherical smooth surface of EMP showed good powder flow properties and acceptable percentage content uniformity (> 95%). Amounts of FP deposited in cascade assembly using USP-modified IP with the Breezhaler® device was significantly higher (1.32-fold) as compared with the Handihaler® device. Moreover, USP-modified IP showed better deposition as compared with USP IP. Additionally, both inhaler devices showed a satisfactory delivered dose (> 105%) for FP using modified glass sampling apparatus at a flow rate of 60 L/min for 2 s. It was interesting to note that not only formulation properties but also IP geometry and device resistance have significant impact on DPI deposition pattern. This study is a first detailed account of aerodynamic performance of FP using USP-modified IP and USP-modified glass sampling apparatus. Thus, it can be of potential importance for both the academic and industry perspective.

Development of High-Strength Extended-Release Multiparticulate System by Crystallo-co-agglomeration Technique with Integration of Central Composite Design.

The number of unit operations to be followed in the preparation of tablets was cumbersome and may introduce material as well as process-related critical parameters which may negatively affect the quality of final formulation. The hypothesis of the present research was to develop directly compressible, high-strength extended-release spherical agglomerates of talc containing indapamide by crystallo-co-agglomeration technique. Hydroxypropyl methylcellulose 15 cps and polyethylene glycol 6000 were used to impart the desired sphericity, strength, and deformability to agglomerates, respectively. Ethyl cellulose 10 cps was used to improve the strength of agglomerates and achieve extended release. Design of experiment (rotatable central composite design) was implemented for the elucidation of the effect of type and quantity of polymers on quality attributes of agglomerates. Prepared agglomerates were evaluated for morphological, micromeritic, mechanical, and drug release properties. A satisfactory yield (> 97%, wt/wt), better crushing strength, and low friability of agglomerates indicated good processing and handling characteristics. Compatibility and reduced crystallinity of indapamide in agglomerates were confirmed by spectroscopic and X-ray diffraction studies. Formation of the miniscular dosage form and hydrophobicity of talc were the key factors observed in controlling and extending the drug release (up to 6 h) from agglomerates. Hence, the developed crystallo-co-agglomeration technique could be successfully used for the preparation of directly compressible high-strength extended-release spherical agglomerates of indapamide.

HME-assisted formulation of taste-masked dispersible tablets of cefpodoxime proxetil and roxithromycin.

Objectives: Antibiotics are the most commonly administered medications among pediatric patients. However most of the time, accurate dose administration to children becomes a problem due to the extremely bitter taste. Cefpodoxime proxetil (CP) and roxithromycin (ROX) are antibiotics often prescribed to the pediatric population and have a bitter taste. Marketed formulations of these drugs are dry suspension and/or tablets. The lyophilization method involves various steps and thus is time consuming and expensive. The objective of this study was to mask the bitter taste of CP and ROX without compromising the solubility and drug release profile compared to marketed formulations, as well as to overcome the disadvantages associated with the currently used lyophilization technique. Methods: Hot melt extrusion (HME) technology was used to process CP and ROX individually with Eudragit E PO polymer. The extrudates obtained were characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry. The powdered extrudates were formulated as dispersible tablets and evaluated for in vitro and in vivo taste-masking efficiency. Results: The tablets prepared in this study showed comparable dissolution profiles but the taste-masking efficiency was significantly enhanced compared to the marketed tablets of CP and ROX. The results of in vivo human taste-masking evaluation were also in agreement with the in vitro taste-masking studies. Conclusion: The current work presents solvent-free, scalable, and continuous HME technology for addressing the bitter taste issues of CP and ROX. The disadvantages associated with the currently used lyophilization technique were overcome by developing the formulations using HME technology.

Design, development, and in-vitro/in-vivo evaluation of docetaxel-loaded PEGylated solid lipid nanoparticles in prostate cancer therapy.

Docetaxel (DOC) is a potent anticancer molecule widely used to treat various cancers. However, its therapeutic efficacy as a potential anticancer agent has been limited owing to poor aqueous solubility, short circulation time, rapid reticuloendothelial system uptake, and high renal clearance, which consecutively showed poor bioavailability. In the present investigation, we developed polyethylene glycol (PEG) decorated solid lipid nanoparticles (SLN) using the solvent diffusion method to increase the biopharmaceutical properties of DOC. PEG monostearate (SA-PEG2000) was initially synthesized and characterized using various analytical techniques. Afterwards, DOC-loaded SLN was synthesized with and without SA-PEG2000and systematically characterized for in-vitro and in-vivo properties. Spherical-shaped SA-PEG2000-DOC SLN showed hydrodynamic diameter and zeta potential of 177 nm and -13 mV, respectively. During the in-vitro release study DOC-loaded SLN showed a controlledrelease of approximately 54.35 % ± 5.46 within 12 h with Higuchi release kinetics in the tumor microenvironment (pH 5.5).In an in-vitro cytotoxicity study,SA-PEG2000-DOC SLN showedsignificantlylower IC50values(p < 0.001)compared to DOC-SLN and DOC aloneagainst prostate cancer cell lines (PC-3). Similarly, an in-vitro cellular uptake study showed a significant increase in intracellular DOC concentration for SA-PEG2000-DOC SLN. Additionally, inin-vivostudies,PEGylated SLN of DOC showed around 2- and 15-fold increase in the maximum concentration of drug (Cmax) and area under the curve (AUC), respectively, as compared to plain DOC solution due to the uniquehydrophilicity and hydrophobicity balance and electrical neutrality of specially designed PEG architect. The biological half-life (t1/2) and mean residence time (MRT) was found to increase from 8.55 and 11.43 to 34.96 and 47.68 h, respectively, with SA-PEG2000-DOC SLN. Moreover, the bio-distribution study indicates high DOC concentration in the plasma which signifies the more pronounced blood residence time of SA-PEG2000-DOC SLN. In a nutshell, SA-PEG2000-DOC SLNwasfound to bea promising and efficient drug delivery platform for the management of Metastatic Prostate cancer.

Delocalized Lipophilic Cation Triphenyl Phosphonium: Promising Molecule for Mitochondria Targeting.

The mitochondria are a dynamic powerhouse organelle that contributes greatly to cancer therapy. Solving the current problems that occur mostly in chemotherapy and diagnosis of various cancers targeting the Mitochondria is an implying approach. In this review, it is discussed how the tethering of mitochondrial-targeting moieties to chemotherapeutics, fluorescent dyes and photothermal molecules can enhance the anticancer effect. The most extensively used mitochondrial targeting conjugate is Triphenyl phosphonium (TPP), which is a delocalized lipophilic cation that gets easily accumulated via the endocytosis mechanism due to the decreased mitochondrial membrane potential of the cancer cell. Credited for this characteristic, TPP has been extensively investigated in targeting mitochondria and delivery of cancer theranostics. This mitochondrial targeting strategy attracted great attention in cancer targeting nanotechnology. The TPP based nanoformulation have exhibited amplified therapeutic outcomes in the treatment of various cancer. Thus, TPP is an ultimate carrier with magnificent potential as a mitochondrial targeting agent.

Preparation and Optimization of Liposome Containing Thermosensitive In Situ Nasal Hydrogel System for Brain Delivery of Sumatriptan Succinate.

Drug absorption is improved by the intranasal route's wide surface area and avoidance of first-pass metabolism. For the treatment of central nervous system diseases such as migraine, intranasal administration delivers the medication to the brain. The study's purpose was to develop an in situ nasal hydrogel that contained liposomes that were loaded with sumatriptan succinate (SS). A thin-film hydration approach was used to create liposomes, and a 32 factorial design was used to optimize them. The optimized liposomes had a spherical shape, a 171.31 nm particle size, a high drug encapsulation efficiency of 83.54%, and an 8-h drug release of 86.11%. To achieve in situ gel formation, SS-loaded liposomes were added to the liquid gelling system of poloxamer-407, poloxamer-188, and sodium alginate. The final product was tested for mucoadhesive strength, viscosity, drug content, gelation temperature, and gelation time. Following intranasal delivery, in vivo pharmacokinetic investigations showed a significant therapeutic concentration of the medication in the brain with a Cmax value of 167 ± 78 ng/mL and an area under the curve value of 502 ± 63 ng/min·mL. For SS-loaded liposomal thermosensitive nasal hydrogel, significantly higher values of the nose-to-brain targeting parameters, that is, drug targeting index (2.61) and nose-to-brain drug direct transport (57.01%), confirmed drug targeting to the brain through the nasal route. Liposomes containing thermosensitive in situ hydrogel demonstrated potential for intranasal administration of SS.

Development of photostable gastro retentive formulation for nifedipine using low-density polypropylene microporous particles.

The aim of this study was to develop photostable gastro retentive formulation for nifedipine loading into low-density polypropylene microporous particles (Accurel MP 1000®) by a solvent evaporation technique using the 3² factorial design. Yield, drug loading, surface topography, thermal properties, crystal characteristics, photostability and in vitro drug release were studied. Optimized microparticles formulated into a capsule were evaluated for the dissolution study and compared with marketed formulation. Higher values of T(50%), time required for 50% degradation of drug with threefold and 1.5-fold decrease in degradation rate constant (K) under UV and fluorescent lamp were observed for the microparticles, respectively, as compared to pure nifedipine indicated remarkable improved photostability. Microparticles showed good floating ability in 0.1N HCl with initial burst release (16-29%) followed by the zero-order drug release up to 8 h. The capsule formulation followed the ideal modified release pattern.

3D printing of pharmaceuticals: approach from bench scale to commercial development.

Background: The three-dimensional (3D) printing is paradigm shift in the healthcare sector. 3D printing is platform technologies in which complex products are developed with less number of additives. The easy development process gives edge over the conventional methods. Every individual needs specific dose treatment. 'One size fits all' is the current traditional approach that can shift to more individual specific in 3D printing. The present review aims to cover different perspectives regarding selection of drug, polymer and technological aspects for 3D printing. With respect to clinical practice, regulatory issue and industrial potential are also discussed in this paper. Main body: The individualization of medicines with patient centric dosage form will become reality in upcoming future. It provides individual's need of dose by considering genetic profile, physiology and diseased condition. The tailormade dosages with unique drug loading and release profile of different geometrical shapes and sizes can easily deliver therapeutic dose. The technology can fulfill growing demand of efficiency in the dose accuracy for the patient oriented sectors like pediatric, geriatric and also easy to comply with cGMP requirements of regulated market. The clinical practice can focus on prescribing each individual's necessity of dose. Conclusion: In the year 2015, FDA approved first 3D printed drug product, which is initiator in the new phase of manufacturing of pharmaceuticals. The tailormade formulations can be made in future for personalized medications. Regulatory approval from agencies can bring the 3DP product into the market. In the future, formulators can bring different sector-specific products for personalized need through 3DP pharmaceutical product.

Formulation and Characterization of Nanostructured Lipid Carriers of Rizatriptan Benzoate-Loaded In Situ Nasal Gel for Brain Targeting.

Intranasal route provides large surface area, avoids first-pass metabolism, and results in improved drug absorption. Intranasal delivery targets the drug to the brain for treatment of central nervous diseases viz migraine. The objective of the study was to formulate in situ nasal gel containing rizatriptan benzoate (RB)-loaded nanostructured lipid carriers (NLCs). NLCs were prepared by melt-emulsification ultrasonication method and optimized using 32 factorial design. Optimized NLCs were spherical with particle size of 189 nm, high drug encapsulation efficiency (84.5%), and 83.9% drug release at the end of 24 h. RB-loaded NLCs were incorporated into the liquid Carbopol 934P and Poloxamer 407 liquid gelling system to obtain in situ gel formation. The resultant product was assessed for gelling capacity, viscosity, and mucoadhesive strength. In vivo pharmacokinetic studies revealed significant therapeutic concentration of drug in the brain following intranasal administration with Cmax value of 5.1 ng/mL and area under the curve value of 829 ng/(min·mL). Significantly higher values of nose to brain targeting parameters, namely, drug targeting index (2.76) and nose to brain drug direct transport (63.69%) for RB-NLCs in situ nasal gel, confirmed drug targeting to brain through nasal route. The ex vivo nasal toxicity study showed no sign of toxicity to the nasal mucosa. Thus, the application of lipid carrier-loaded in situ gel proved potential for intranasal delivery of RB over the conventional gel formulations for efficient brain targeting.

Improved bioavailability of orally administered andrographolide from pH-sensitive nanoparticles.

Andrographolide, a major bioactive phytoconstituent derived from Androgaphis paniculata that is safe and beneficial in several ailments, was formulated into pH-sensitive nanoparticle suspension with a view of improving its oral bioavailability. The andrographolide-loaded pH-sensitive nanoparticles were prepared by nanoprecipitation technique using Eudragit® EPO (cationic poly methacrylate copolymer). The 3(2) factorial design was used to optimize the amount of polymer and stabilizer (Pluronic® F-68). The optimized batch obtained using 0.45% w/v of Eudragit® EPO and 0.6% w/v of Pluronic® F-68 showed high-encapsulation efficiency of 93.8±0.67% with particle size of 255±9 nm and zeta potential of 29.3±3.4 mV. The bioavailability of andrographolide from optimized nanoparticles and pure andrographolide was assessed in male Wistar albino rats at a dose of 10 mg/kg. As compared to the pure andrographolide, almost 2.2 and 3.2-fold increase in AUC0-∞, Cmax and 121.53% increase in relative bioavailability were observed for andrographolide from pH-sensitive nanoparticles (P<0.05). Shorter Tmax by about fourfold difference were observed with 2.2-fold decrease in Cl/F. The improved dissolution rate owing to its reduced particle size, increased surface area and reduced diffusion layer thickness may have contributed to oral bioavailability. The results clearly indicate the potential of pH-sensitive nanoparticles for oral delivery of low-bioavailability phytoconstituents such as andrographolide.

Preparation and evaluation of talc agglomerates obtained by wet spherical agglomeration as a substrate for coating.

The present research was aimed at the preparation of spherical agglomerates of talc (SAT) by wet spherical agglomeration (WSA) and evaluation as inert core/substrate for coating. Talc being an inert and inexpensive excipient was used in the design of spherical agglomerates. To evaluate agglomerate performance, comparison was made with sugar spheres (SS), having a size 1200 µm, for surface morphology, micromeritics, mechanical, compressional and drug release properties. Surface morphology studied by scanning electron microscopy (SEM) and optical profilometry have shown smooth surface of SAT compared to SS. Shape and sphericity analysis of both showed aspect ratio close to 1. Flowability of SAT was similar to SS. Although, crushing force of SAT was significantly less than SS (p = 0.05), friability studies revealed that it was satisfactory. Compressibility studies showed plastic deformation of SAT unlike SS. Both SAT and SS had comparable drug and polymer layering efficiency, with better surface smoothness in SAT than SS, as confirmed from optical profilometry. Thus, SAT, similar to SS, can be used as a substrate for coating due to its comparable surface topography, micromeritics, adequate crushing resistance and satisfactory drug and polymer layering efficiency.

An overview of regulations for bioequivalence assessment of locally acting orally inhaled drug products for the United States, Europe, Canada, and India.

INTRODUCTION: Bioequivalence is established by comparing the bioequivalence study results of generic drugs with the reference listed drug. Several global regulatory agencies have published the guidance for locally acting orally inhaled drug products (OIDPs) for bioequivalence approaches. AREAS COVERED: The prime intent of the present article is to compare the regulatory guidance for bioequivalence assessment of locally acting OIDPs published by global regulatory authorities. Regulatory recommendations on bioequivalence were based on assessment for different parameters such as inhaler device, formulation, reference product selection, in-vitro, and in-vivo studies. The United States Food and Drug Administration and Health Canada suggest an aggregated weight of evidence approach and the European Medicines Agency promotes a stepwise approach, whereas though the Indian authorities have not published guidance specifically on OIDPs but provided guidelines for bioavailability and bioequivalence studies. EXPERT OPINION: For OIDPs, currently, there is no universally adopted methodology, and regulatory guidance has not been globally harmonized. By understanding and comparing bioequivalence recommendations for different regions, we can create more sensitive, and economic evaluation methods for OIDPs. This could open more alternatives of safe, effective generic OIDPs to the public.

Studies on nonionic surfactant bilayer vesicles of ciclopirox olamine.

CONTEXT: Niosomal delivery can prove an alternative to improve the poor skin penetration and residence of the topical antifungal drugs that account for the long treatment regimes in cutaneous mycosis. OBJECTIVE: To investigate niosomes as carriers for dermal delivery of ciclopirox olamine (CPO), a broad spectrum antifungal drug. MATERIALS AND METHODS: Niosomes were prepared by ethanol injection method using Span 60, cholesterol, diacetyl phosphate according to 3(2) factorial design and evaluated for physicochemical parameters, in vitro and ex vivo deposition in skin and stability study. RESULTS: Unilamellar CPO niosomes of size 170-280 nm, entrapment efficiency 38-68%, and sufficient electrokinetic stability were obtained. Percent drug deposition in artificial membrane varied from 12.75 to 92.74. Deposition of CPO into rat skin from niosomal dispersion and its gel was significantly higher than that of plain CPO solution and its marketed product. Obtained niosomes possessed sufficient stability on storage. DISCUSSION: Increasing amounts of Span 60 and cholesterol increase the vesicle size probably because of entrapment of CPO-ionized molecules in the aqueous compartment and interaction of its unionized counterpart with the bilayer constituents leading to increase in bilayer thickness. Consequently, the percent entrapment efficiency also increased. However, increasing Span 60 levels decreased the in vitro percent drug deposition. This might be attributed to the larger size of vesicles produced by high amounts of surfactant that showed poor deposition. The optimized batch possessed sufficient stability. CONCLUSIONS: The results of this investigation suggest that niosomes are promising tools for cutaneous retention of CPO.

Stomach-specific controlled release gellan beads of acid-soluble drug prepared by ionotropic gelation method.

The purpose of the present work was the development and evaluation of stomach-specific controlled release mucoadhesive drug delivery system prepared by ionotropic gelation of gellan beads, containing acid-soluble drug amoxicillin trihydrate, using 3(2) factorial design with concentration of gellan gum and quantity of drug as variables. The study showed that beads prepared in alkaline cross-linking medium have higher entrapment efficiency than the acidic cross-linking medium. The entrapment efficiency was in the range of 32% to 46% w/w in acidic medium, which increased up to 60% to 90% w/w in alkaline medium. Batches with lowest, medium, and highest drug entrapment were subjected to chitosan coating to form a polyelectrolyte complex film. As polymer concentration increases, entrapment efficiency and particle size increases. Scanning electron microscopy revealed spherical but rough surface due to leaching of drug in acidic cross-linking solution, dense spherical structure in alkaline cross-linking solution, and rough surface of chitosan-coated beads with minor wrinkles. The in vitro drug release up to 7 h in a controlled manner following the Peppas model (r = 0.9998). In vitro and in vivo mucoadhesivity study showed that beads have good mucoadhesivity and more than 85% beads remained adhered to stomach mucosa of albino rat even after 7 h. In vitro growth inhibition study showed complete eradication of Helicobacter pylori. These results indicate that stomach-specific controlled release mucoadhesive system of amoxicillin gellan beads may be useful in H. pylori treatment.