Journal of Drug Delivery The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Investigation of Diffusion Characteristics through Microfluidic Channels for Passive Drug Delivery Applications Thu, 26 May 2016 13:48:23 +0000 Microfluidics has many drug delivery applications due to the ability to easily create complex device designs with feature sizes reaching down to the 10s of microns. In this work, three different microchannel designs for an implantable device are investigated for treatment of ocular diseases such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy. Devices were fabricated using polydimethylsiloxane (PDMS) and soft lithography techniques, where surface chemistry of the channels was altered using 2-[methoxy(polyethyleneoxy)propyl]trimethoxysilane (PEG-silane). An estimated delivery rate for a number of common drugs was approximated for each device through the ratio of the diffusion coefficients for the dye and the respective drug. The delivery rate of the model drugs was maintained at a physiological condition and the effects of channel design and surface chemistry on the delivery rate of the model drugs were recorded over a two-week period. Results showed that the surface chemistry of the device had no significant effect on the delivery rate of the model drugs. All designs were successful in delivering a constant daily dose for each model drug. Marcus J. Goudie, Alyssa P. Ghuman, Stephanie B. Collins, Ramana M. Pidaparti, and Hitesh Handa Copyright © 2016 Marcus J. Goudie et al. All rights reserved. Design and Evaluation of Voriconazole Loaded Solid Lipid Nanoparticles for Ophthalmic Application Thu, 12 May 2016 09:04:18 +0000 Voriconazole is a second-generation antifungal agent with excellent broad spectrum of antifungal activity commercially available for oral and intravenous administration. Systemic administration of voriconazole is associated with side effects including visual and hepatic abnormalities. This study assessed the feasibility of using solid lipid nanoparticles for ocular delivery of voriconazole adopting stearic acid as lipidic material, tween 80 as a stabilizer, and Carbopol 934 as controlled release agent and for increasing the precorneal residence time in eye. The systems were prepared using two different methods, that is, ultrasonication method and microemulsion technique. The results indicated that the larger particle size of SLNs was found with microemulsion technique ( nm to ) compared to SLN prepared with ultrasonication method ( nm to  nm). The polydispersity index values were less than 0.3 for all formulations and zeta potential of the prepared formulations by these two methods varied from − mV to − mV. Powder X-ray diffraction and differential scanning calorimetry indicated decrease in crystallinity of drug. The in vitro release study and the SLN formulations prepared with ultrasonication method demonstrated sustained release up to 12 hours. This study demonstrated that SLN prepared by ultrasonication method is more suitable than microemulsion technique without causing any significant effect on corneal hydration level. Anubha Khare, Inderbir Singh, Pravin Pawar, and Kanchan Grover Copyright © 2016 Anubha Khare et al. All rights reserved. Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations Sun, 17 Apr 2016 11:01:41 +0000 Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and −20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1. Faithful Makita-Chingombe, Hilliard L. Kutscher, Sara L. DiTursi, Gene D. Morse, and Charles C. Maponga Copyright © 2016 Faithful Makita-Chingombe et al. All rights reserved. PEG-Immobilized Keratin for Protein Drug Sequestration and pH-Mediated Delivery Wed, 20 Jan 2016 12:15:32 +0000 Protein drugs like growth factors are promising therapeutics for damaged-tissue repair. Their local delivery often requires biomaterial carriers for achieving the therapeutic dose range while extending efficacy. In this study, polyethylene glycol (PEG) and keratin were crosslinked and used as sponge-like scaffolds (KTN-PEG) to absorb test proteins with different isoelectric points (pI): albumin (~5), hemoglobin (~7), and lysozyme (~11). The protein release kinetics was influenced by charge at physiological pH 7.4. The keratin network, with pI 5.3, electrostatically attracted lysozyme and repulsed albumin generating the release rate profile: albumin > hemoglobin > lysozyme. However, under acidic conditions (pH 4), all proteins including keratins were positively charged and consequently intermolecular repulsion altered the release hierarchy, now determined by size (MW) diffusion: lysozyme (14 kDa) > hemoglobin (64 kDa) > albumin (66 kDa). Vascular endothelial growth factor C (VEGF-C), with properties comparable to lysozyme, was absorbed into the KTN-PEG scaffold. Endothelial cells cultured on this substrate had significantly larger numbers than on scaffolds without VEGF-C suggesting that the ionically bound and retained growth factor at neutral pH indirectly increased acute cell attachment and viability. PEG and keratin based sequestrations of proteins with basic pIs are therefore a feasible strategy with potential applications for selective biologics delivery. Roche C. de Guzman and Sina Y. Rabbany Copyright © 2016 Roche C. de Guzman and Sina Y. Rabbany. All rights reserved. Reassessing the Role of Intra-Arterial Drug Delivery for Glioblastoma Multiforme Treatment Sun, 27 Dec 2015 12:20:49 +0000 Effective treatment for glioblastoma (GBM) will likely require targeted delivery of several specific pharmacological agents simultaneously. Intra-arterial (IA) delivery is one technique for targeting the tumor site with multiple agents. Although IA chemotherapy for glioblastoma (GBM) has been attempted since the 1950s, the predicted benefits remain unproven in clinical practice. This review focuses on innovative approaches to IA drug delivery in treating GBM. Guided by novel in vitro and in vivo optical measurements, newer pharmacokinetic models promise to better define the complex relationship between background cerebral blood flow and drug injection parameters. Advanced optical technologies and tracers, unique nanoparticles designs, new cellular targets, and rational drug formulations are continuously modifying the therapeutic landscape for GBM. Personalized treatment approaches are emerging; however, such tailored approaches will largely depend on effective drug delivery techniques and on the ability to simultaneously deliver multidrug regimens. These new paradigms for tumor-selective drug delivery herald dramatic improvements in the effectiveness of IA chemotherapy for GBM. Therefore, within this context of so-called “precision medicine,” the role of IA delivery for GBM is thoroughly reassessed. Jason A. Ellis, Matei Banu, Shaolie S. Hossain, Rajinder Singh-Moon, Sean D. Lavine, Jeffrey N. Bruce, and Shailendra Joshi Copyright © 2015 Jason A. Ellis et al. All rights reserved. Impact of Computerized Order Entry to Pharmacy Interface on Order-Infusion Pump Discrepancies Wed, 18 Nov 2015 07:44:55 +0000 Background. The ability of safety technologies to decrease errors, harm, and risk to patients has yet to be demonstrated consistently. Objective. To compare discrepancies between medication and intravenous fluid (IVF) orders and bedside infusion pump settings within a pediatric intensive care unit (PICU) before and after implementation of an interface between computerized physician order entry (CPOE) and pharmacy systems. Methods. Within a 72-bed PICU, medication and IVF orders in the CPOE system and bedside infusion pump settings were collected. Rates of discrepancy were calculated and categorized by type. Results were compared to a study conducted prior to interface implementation. Expansion of PICU also occurred between study periods. Results. Of 455 observations, discrepancy rate decreased for IVF () compared to previous study. Overall discrepancy rate for medications was unchanged; however, medications infusing without an order decreased (), and orders without corresponding infusion increased (). Conclusions. Following implementation of an interface between CPOE and pharmacy systems, fewer discrepancies between IVF orders and infusion pump settings were observed. Discrepancies for medications did not change, and some types of discrepancies increased. In addition to interface implementation, changes in healthcare delivery and workflow related to ICU expansion contributed to observed changes. Rebecca A. Russell, David Triscari, Kathy Murkowski, and Matthew C. Scanlon Copyright © 2015 Rebecca A. Russell et al. All rights reserved. Investigation of Fatty Acid Ketohydrazone Modified Liposome’s Properties as a Drug Carrier Mon, 16 Nov 2015 07:48:02 +0000 pH-responsive liposomes were prepared by modifying the liposome with acid-cleaving amphiphiles. Palmitic ketohydrazone (P-KH) or stearic ketohydrazone (S-KH), composed of hydrophilic sugar headgroup and hydrophobic acyl chain, was used as a modifier of the DMPC liposome. Because the ketohydrazone group of P-KH or S-KH was cleaved at low pH conditions (<pH 5.0), the delivery of the P-KH modified liposomes was observed probably via an endocytic pathway. The membrane properties of these liposomes were characterized, focusing on the variation of both polarity (measured by Laurdan) and membrane fluidity (measured by DPH) at low pH condition. The interface of the P-KH modified liposome at acidic pH was found to become more hydrophobic and less fluidic as compared with that at neutral pH; that is, P-KH modified liposome became more rigid structure. Therefore, it seems that the P-KH modified liposome could protect encapsulated drugs from the enzymes in the lysosome. This study shows the novel approach about design of pH-responsive liposomes based on the membrane properties. Keita Hayashi, Madoka Kiriishi, Keishi Suga, Yukihiro Okamoto, and Hiroshi Umakoshi Copyright © 2015 Keita Hayashi et al. All rights reserved. Characterization and Compatibility Studies of Different Rate Retardant Polymer Loaded Microspheres by Solvent Evaporation Technique: In Vitro-In Vivo Study of Vildagliptin as a Model Drug Thu, 12 Nov 2015 09:02:34 +0000 The present study has been performed to microencapsulate the antidiabetic drug of Vildagliptin to get sustained release of drug. The attempt of this study was to formulate and evaluate the Vildagliptin loaded microspheres by emulsion solvent evaporation technique using different polymers like Eudragit RL100, Eudragit RS100, Ethyl cellulose, and Methocel K100M. In vitro dissolution studies were carried out in 0.1 N HCl for 8 hours according to USP paddle method. The maximum and minimum drug release were observed as 92.5% and 68.5% from microspheres, respectively, after 8 hours. Release kinetics were studied in different mathematical release models to find out the linear relationship and release rate of drug. The SEM, DSC, and FTIR studies have been done to confirm good spheres and smooth surface as well as interaction along with drug and polymer. In this experiment, it is difficult to explain the exact mechanism of drug release. But the drug might be released by both diffusion and erosion as the correlation coefficient () best fitted with Korsmeyer model and release exponent () was 0.45–0.89. At last it can be concluded that all in vitro and in vivo experiments exhibited promising result to treat type II diabetes mellitus with Vildagliptin microspheres. Irin Dewan, Swarnali Islam, and Md. Sohel Rana Copyright © 2015 Irin Dewan et al. All rights reserved. Design and Characterization of Buccoadhesive Liquisolid System of an Antihypertensive Drug Thu, 22 Oct 2015 08:17:44 +0000 Nifedipine is an antihypertensive BCS class II drug which has poor bioavailability when given orally. The objective of the present study was to increase the bioavailability of nifedipine, by formulation and evaluation of a buccoadhesive liquisolid system using magnesium aluminium silicate (Neusilin) as both carrier and coating material and dissolution media were selected based on the solubility studies. A mixture of carboxymethylcellulose sodium and carbomer was used as mucoadhesive polymers. Buccoadhesive tablets were prepared by direct compression. FTIR studies confirmed no interaction between drug and excipients. XRD studies indicated change/reduction in crystallinity of drug. The powder characteristics were evaluated by different flow parameters to comply with pharmacopoeial specifications. The dissolution studies for liquisolid compacts and tablet formulations were carried out and it was found that nifedipine liquisolid tablets formulated from bioadhesive polymers containing 49% liquisolid system, 17.5% carbomer, and 7.5% carboxymethylcellulose sodium showed the best results in terms of dissolution properties. Prepared formulation batches were evaluated for swelling, bioadhesion strength, ex vivo residence time, and permeability studies. The optimized batch was showing promising features of the system. Formulating nifedipine as a buccoadhesive tablet allows reduction in dose and offers better control over the plasma levels. Nilesh P. Kala, Divyesh H. Shastri, and Pragna K. Shelat Copyright © 2015 Nilesh P. Kala et al. All rights reserved. Dosing-Time Dependent Effects of Sodium Nitroprusside on Cerebral, Renal, and Hepatic Catalase Activity in Mice Sun, 15 Mar 2015 07:58:42 +0000 To investigate the time dependence of sodium nitroprusside- (NPS-) induced oxidative effects, the authors study the variation of the antioxidant enzyme CAT activity in various tissues after the administration of a single 2.5 mg/kg dose of SNP or sodium chloride (NaCl 0.9%). For each of the two dosing times (1 and 13 hours after light onset, HALO, which correspond to the beginning of diurnal rest span and of nocturnal activity span of mice, resp.), brain, kidney, and liver tissues were excised from animals at 0, 1, 3, 6, 9, 12, 24, and 36 h following the drug administration and CAT activity was assayed. The results suggest that SNP-induced stimulation of CAT activity is greater in all three tissues when the drug is administered at 1 HALO than at 13 HALO. Two-way ANOVA revealed that CAT activity significantly () varied as a function of the sampling time but not of the treatment in all three tissues. Moreover, a statistically significant () interaction between the organ sampling-time and the SNP treatment was revealed in kidney regardless of the dosing time, whereas a highly significant () interaction was validated in liver only in animals injected at 13 HALO. Mamane Sani, Hichem Sebai, Roberto Refinetti, Mohan Mondal, Néziha Ghanem-Boughanmi, Naceur A. Boughattas, and Mossadok Ben-Attia Copyright © 2015 Mamane Sani et al. All rights reserved. Formulation Development and Evaluation of Fast Disintegrating Tablets of Salbutamol Sulphate, Cetirizine Hydrochloride in Combined Pharmaceutical Dosage Form: A New Era in Novel Drug Delivery for Pediatrics and Geriatrics Wed, 25 Feb 2015 09:48:12 +0000 The objective of the present study was to prepare the fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form for respiratory disorders such as bronchitis, asthma, and coughing for pediatrics and geriatrics. The tablets were prepared by direct compression technique. Superdisintegrant such as Sodium Starch Glycolate was optimized as 4% on the basis of least disintegration time. Different binders such as MCC and PVP K-30 were optimized along with optimized superdisintegrant concentration. 1% MCC was selected as optimum binder concentration on the basis of least disintegration time. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time, and drug content uniformity. Optimized formulation was further evaluated by in vitro dissolution test, drug-excipient compatibility, and accelerated stability study. Percent weight variation and content uniformity were within the acceptable limit. The friability was less than 1%. The wetting time and disintegration time were practically good for all formulations. FTIR studies and accelerated stability study showed that there was no interaction between the drug and excipients. It was concluded that, by employing commonly available pharmaceutical excipients such as superdisintegrants, hydrophilic and swellable excipients and proper filler, a fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form, were formulated successfully with desired characteristics. Deepak Sharma, Gurmeet Singh, Dinesh Kumar, and Mankaran Singh Copyright © 2015 Deepak Sharma et al. All rights reserved. Calcium Alginate-Neusilin US2 Nanocomposite Microbeads for Oral Sustained Drug Delivery of Poor Water Soluble Drug Aceclofenac Sodium Mon, 23 Feb 2015 13:46:29 +0000 The aim of the present study was to formulate and investigate the calcium alginate- (CA-) Neusilin US2 nanocomposite microbeads containing preconcentrate of aceclofenac sodium (ACF-Na) liquid microemulsion (L-ME) for enhancement of oral bioavailability. The preconcentrate L-ME is prepared by using Labrafac PG, Labrasol, and Span 80 as oil, surfactant, and cosurfactant, respectively. The solid CA nanocomposite microbeads of L-ME prepared by microemulsification internal gelation technique using sodium alginate (SA) gelling agent, Neusilin US2 as adsorbent, and calcium chloride as crosslinking agent. L-ME has good thermodynamic stability; globule size was found to be 32.4 nm with polydispersity index 0.219 and −6.32 mV zeta potential. No significant interactions of excipients, drug in the formulations observed by FT-IR, DSC and XPRD. The concentration of SA and Neusilin US2 influences the flow properties, mean particle size, mechanical strength, drug entrapment efficiency, and percentage of drug release. All the formulations show minimum drug release in simulated gastric fluid (SGF) pH 1.2 for initial 2 h, maximum drug release in pH 6.8 phosphate buffer solution (PBS) at 6 h, followed by sustaining in simulated intestinal fluid (SIF) of pH 7.4 up to 12 h. The interaction of SA with Neusilin US2 creates a thick thixotropic gel network structure which acts as barrier to control the release of drug in the alkaline pH environment. Neusilin US2 is a novel filler used to convert L-ME into solid nanocomposite microbeads to enhance dissolution rate of poor water soluble drugs sustaining the drug release for prolonged period of time. Manjanna Kolammanahalli Mallappa, Rajesh Kesarla, and Shivakumar Banakar Copyright © 2015 Manjanna Kolammanahalli Mallappa et al. All rights reserved. Formulation and Evaluation of Optimized Oxybenzone Microsponge Gel for Topical Delivery Wed, 18 Feb 2015 17:34:39 +0000 Background. Oxybenzone, a broad spectrum sunscreen agent widely used in the form of lotion and cream, has been reported to cause skin irritation, dermatitis, and systemic absorption. Aim. The objective of the present study was to formulate oxybenzone loaded microsponge gel for enhanced sun protection factor with reduced toxicity. Material and Method. Microsponge for topical delivery of oxybenzone was successfully prepared by quasiemulsion solvent diffusion method. The effects of ethyl cellulose and dichloromethane were optimized by the 32 factorial design. The optimized microsponges were dispersed into the hydrogel and further evaluated. Results. The microsponges were spherical with pore size in the range of 0.10–0.22 µm. The optimized formulation possesses the particle size and entrapment efficiency of 72 ± 0.77 µm and 96.9 ± 0.52%, respectively. The microsponge gel showed the controlled release and was nonirritant to the rat skin. In creep recovery test it had shown highest recovery indicating elasticity. The controlled release of oxybenzone from microsponge and barrier effect of gel result in prolonged retention of oxybenzone with reduced permeation activity. Conclusion. Evaluation study revealed remarkable and enhanced topical retention of oxybenzone for prolonged period of time. It also showed the enhanced sun protection factor compared to the marketed preparation with reduced irritation and toxicity. Atmaram P. Pawar, Aditya P. Gholap, Ashwin B. Kuchekar, C. Bothiraja, and Ashwin J. Mali Copyright © 2015 Atmaram P. Pawar et al. All rights reserved. Formulation and In Vitro Evaluation of Bilayer Tablets of Nebivolol Hydrochloride and Nateglinide for the Treatment of Diabetes and Hypertension Wed, 14 Jan 2015 07:05:49 +0000 Diabetes mellitus (DM) and hypertension are two common diseases that often coexist. The most common cause of death in the diabetic patient is heart disease. In the present investigation we combine Nebivolol and Nateglinide for better patient compliance. IR layer was formulated using various superdisintegrants like Crospovidone, Croscarmellose sodium, and sodium starch glycolate and SR layer was formulated using polymers and gums like HPMC E15, ethyl cellulose, Gaur gum, and Xanthan gum. The disintegration and dissolution study of both layers showed that inclusion of surfactant (sodium lauryl sulphate) to the tablet formulation (IR) and dissolution medium (SR) enhanced the release of drugs from both layers. Kinetic studies of optimized IR layer (NBL8) and SR layer (N9) showed good linearity with regression coefficient of 0.9714 (Higuchi model) and 0.9931 (zero order kinetics), respectively. The above results reveal that the optimized IR layer of Nebivolol (NBL8) and SR layer of Nateglinide (N9) might be suitable for the treatment of diabetes and hypertension by sequential release of the two drugs in a bilayer tablet. IR-immediate release, SR-sustain release, NBL8-Nebivolol 8, N9-Nateglinide 9. Harika Ryakala, S. Dineshmohan, Alluri Ramesh, and V. R. M. Gupta Copyright © 2015 Harika Ryakala et al. All rights reserved. High-Resolution Imaging of Polyethylene Glycol Coated Dendrimers via Combined Atomic Force and Scanning Tunneling Microscopy Thu, 01 Jan 2015 09:43:05 +0000 Dendrimers have shown great promise as drug delivery vehicles in recent years because they can be synthesized with designed size and functionalities for optimal transportation, targeting, and biocompatibility. One of the most well-known termini used for biocompatibility is polyethylene glycol (PEG), whose performance is affected by its actual conformation. However, the conformation of individual PEG bound to soft materials such as dendrimers has not been directly observed. Using atomic force microscopy (AFM) and scanning tunneling microscopy (STM), this work characterizes the structure adopted by PEGylated dendrimers with the highest resolution reported to date. AFM imaging enables visualization of the individual dendrimers, as well as the differentiation and characterization of the dendrimer core and PEG shell. STM provides direct imaging of the PEG extensions with high-resolution. Collectively, this investigation provides important insight into the structure of coated dendrimers, which is crucial for the design and development of better drug delivery vehicles. Shawn Riechers, Qian Zhong, Nai-Ning Yin, Arpad Karsai, Sandro R. P. da Rocha, and Gang-yu Liu Copyright © 2015 Shawn Riechers et al. All rights reserved. Tumor Angiogenesis Therapy Using Targeted Delivery of Paclitaxel to the Vasculature of Breast Cancer Metastases Sun, 07 Dec 2014 07:13:48 +0000 Breast cancer aberrantly expresses tissue factor (TF) in cancer tissues and cancer vascular endothelial cells (VECs). TF plays a central role in cancer angiogenesis, growth, and metastasis and, as such, is a target for therapy and drug delivery. TF is the cognate receptor of factor VIIa (fVIIa). We have coupled PTX (paclitaxel, also named Taxol) with a tripeptide, phenylalanine-phenylalanine-arginine chloromethyl ketone (FFRck) and conjugated it with fVIIa. The key aim of the work is to evaluate the antiangiogenic effects of PTX-FFRck-fVIIa against a PTX-resistant breast cancer cell line. Matrigel mixed with VEGF and MDA-231 was injected subcutaneously into the flank of athymic nude mice. Animals were treated by tail vein injection of the PTX-FFRck-fVIIa conjugate, unconjugated PTX, or PBS. The PTX-FFRck-fVIIa conjugate significantly reduces microvessel density in matrigel () compared to PBS and unconjugated PTX. The breast cancer lung metastasis model in athymic nude mice was developed by intravenous injection of MDA-231 cells expressing luciferase. Animals were similarly treated intravenously with the PTX-FFRck-fVIIa conjugate or PBS. The conjugate significantly inhibits lung metastasis as compared to the control, highlighting its potential to antagonize angiogenesis in metastatic carcinoma. In conclusion, PTX conjugated to fVIIa is a promising therapeutic approach for improving selective drug delivery and inhibiting angiogenesis. Shijun Zhu, Walter Kisiel, Yang J. Lu, Lars C. Petersen, John M. Ndungu, Terry W. Moore, Ernest T. Parker, Aiming Sun, Dennis C. Liotta, Bassel F. El-Rayes, Daniel J. Brat, James P. Snyder, and Mamoru Shoji Copyright © 2014 Shijun Zhu et al. All rights reserved. Carboxymethyl Cellulose Acetate Butyrate: A Review of the Preparations, Properties, and Applications Thu, 04 Dec 2014 09:09:24 +0000 Carboxymethyl cellulose acetate butyrate (CMCAB) has gained increasing importance in several fields, particularly in coating technologies and pharmaceutical research. CMCAB is synthesized by esterification of CMC sodium salt with acetic and butyric anhydrides. CMCAB mixed esters are relatively high molecular weight (MW) thermoplastic polymers with high glass transition temperatures (Tg). CMCAB ester is dispersible in water and soluble in a wide range of organic solvents, allowing varied opportunity to the solvent choice. It makes application of coatings more consistent and defect-free. Its ability to slow down the release rate of highly water-soluble compounds and to increase the dissolution of poorly soluble compounds makes CMCAB a unique and potentially valuable tool in pharmaceutical and amorphous solid dispersions (ASD) formulations. Mohamed El-Sakhawy, Samir Kamel, Ahmed Salama, and Hebat-Allah Sarhan Copyright © 2014 Mohamed El-Sakhawy et al. All rights reserved. Design and Evaluation of Polyox and Pluronic Controlled Gastroretentive Delivery of Troxipide Wed, 19 Nov 2014 06:06:07 +0000 Objective. Objective of the present work was to develop site-specific gastroretentive drug delivery of Troxipide using polymers Pluronic F127 and Polyox 205 WSR. Troxipide is a novel gastroprotective agent with antiulcer, anti-inflammatory, and mucus secreting properties with elimination half-life of 7.4 hrs. Troxipide inhibits H. pylori-derived urease. It is mainly absorbed from stomach. Methods. 32 factorial design was applied to study the effect of independent variable. Effects of concentration of polymer on dependant variables as swelling index, hardness, and % drug release were studied. Pluronic F127 and Polyox 205 WSR were used as rate controlled polymer. Sodium bicarbonate and citric acid were used as effervescent-generating agent. Results. From the factorial batches, it was observed that formulation F5 (19% Pluronic F127 and 80% Polyox 205 WSR) showed optimum controlled drug release (98.60% ± 1.82) for 10 hrs with ability to float >12 hrs. Optimized formulation characterized by FTIR and DSC studies confirmed no chemical interactions between drug and polymer. Gastroretention for 6 hrs for optimized formulations was confirmed by in vivo X-ray placebo study. Conclusion. Results demonstrated feasibility of Troxipide in the development of gastroretentive site-specific drug delivery. Swati C. Jagdale, Shraddha B. Kamble, Bhanudas S. Kuchekar, and Aniruddha R. Chabukswar Copyright © 2014 Swati C. Jagdale et al. All rights reserved. Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach Thu, 13 Nov 2014 06:00:16 +0000 Low solubility causing low dissolution in gastrointestinal tract is the major problem for drugs meant for systemic action after oral administration, like cinnarizine. Pharmaceutical products of cinnarizine are commercialized globally as immediate release preparations presenting low absorption with low and erratic bioavailability. Approaches to enhance bioavailability are widely cited in the literature. An attempt has been made to review the bioavailability complications and clinical therapeutics of poorly water soluble drug: cinnarizine. The interest of writing this paper is to summarize the pharmacokinetic limitations of drug with special focus on strategies to improvise bioavailability along with effectiveness of novel dosage forms to circumvent the obstacle. The paper provides insight to the approaches to overcome low and erratic bioavailability of cinnarizine by cyclodextrin complexes and novel dosage forms: self-nanoemulsifying systems and buoyant microparticulates. Nanoformulations need to systematically explored in future, for their new clinical role in prophylaxis of migraine attacks in children. Clinical reports have affirmed the role of cinnarizine in migraine prophylaxis. Research needs to be dedicated to develop dosage forms for efficacious bioavailability and drug directly to brain. Smita Raghuvanshi and Kamla Pathak Copyright © 2014 Smita Raghuvanshi and Kamla Pathak. All rights reserved. Preparation and Characterization of Liquisolid Compacts for Improved Dissolution of Telmisartan Sun, 12 Oct 2014 10:47:49 +0000 The objective of the present work was to obtain pH independent and improved dissolution profile for a poorly soluble drug, telmisartan using liquisolid compacts. Liquisolid compacts were prepared using Transcutol HP as vehicle, Avicel PH102 as carrier, and Aerosil 200 as a coating material. The formulations were evaluated for drug excipient interactions, change in crystallinity of drug, flow properties, and general quality control tests of tablets using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), angle of repose, and various pharmacopoeial tests. In vitro dissolution studies were performed at three pH conditions (1.2, 4.5 and 7.4). Stability studies were performed at 40°C and 75% RH for three months. The formulation was found to comply with Indian pharmacopoeial limits for tablets. FTIR studies confirmed no interaction between drug and excipients. XRD and DSC studies indicate change/reduction in crystallinity of drug. Dissolution media were selected based on the solubility studies. The optimized formulation showed pH independent release profile with significant improvement in dissolution compared to plain drug and conventional marketed formulation. No significant difference was seen in the tablet properties, and drug release profile after storage for 3 months. Naveen Chella, Nataraj Narra, and Tadikonda Rama Rao Copyright © 2014 Naveen Chella et al. All rights reserved. The Signature Sequence Region of the Human Drug Transporter Organic Anion Transporting Polypeptide 1B1 Is Important for Protein Surface Expression Thu, 09 Oct 2014 13:47:24 +0000 The organic anion transporting polypeptides (OATPs) encompass a family of membrane transport proteins responsible for the uptake of xenobiotic compounds. Human organic anion transporting polypeptide 1B1 (OATP1B1) mediates the uptake of clinically relevant compounds such as statins and chemotherapeutic agents into hepatocytes, playing an important role in drug delivery and detoxification. The OATPs have a putative 12-transmembrane domain topology and a highly conserved signature sequence (human OATP1B1: DSRWVGAWWLNFL), spanning the extracellular loop 3/TM6 boundary. The presence of three conserved tryptophan residues at the TM interface suggests a structural role for the sequence. This was investigated by site-directed mutagenesis of selected amino acids within the sequence D251E, W254F, W258/259F, and N261A. Transport was measured using the substrate estrone-3-sulfate and surface expression detected by luminometry and confocal microscopy, facilitated by an extracellular FLAG epitope. Uptake of estrone-3-sulfate and the surface expression of D251E, W254F, and W258/259F were both significantly reduced from the wild type OATP1B1-FLAG in transfected HEK293T cells. Confocal microscopy revealed that protein was produced but was retained intracellularly. The uptake and expression of N261A were not significantly different. The reduction in surface expression and intracellular protein retention indicates a structural and/or membrane localization role for these signature sequence residues in the human drug transporter OATP1B1. Jennina Taylor-Wells and David Meredith Copyright © 2014 Jennina Taylor-Wells and David Meredith. All rights reserved. Design Optimization and In Vitro-In Vivo Evaluation of Orally Dissolving Strips of Clobazam Sun, 28 Sep 2014 00:00:00 +0000 Clobazam orally dissolving strips were prepared by solvent casting method. A full 32 factorial design was applied for optimization using different concentration of film forming polymer and disintegrating agent as independent variable and disintegration time, % cumulative drug release, and tensile strength as dependent variable. In addition the prepared films were also evaluated for surface pH, folding endurance, and content uniformity. The optimized film formulation showing the maximum in vitro drug release, satisfactory in vitro disintegration time, and tensile strength was selected for bioavailability study and compared with a reference marketed product (frisium5 tablets) in rabbits. Formulation (F6) was selected by the Design-expert software which exhibited DT (24 sec), TS (2.85 N/cm2), and in vitro drug release (96.6%). Statistical evaluation revealed no significant difference between the bioavailability parameters of the test film (F6) and the reference product. The mean ratio values (test/reference) of (95.87%), (71.42%), (98.125%), and (99.213%) indicated that the two formulae exhibited comparable plasma level-time profiles. Rajni Bala, Sushil Khanna, and Pravin Pawar Copyright © 2014 Rajni Bala et al. All rights reserved. Development of Corn Starch-Neusilin UFL2 Conjugate as Tablet Superdisintegrant: Formulation and Evaluation of Fast Disintegrating Tablets Tue, 23 Sep 2014 05:46:23 +0000 In the present study, corn Starch-Neusilin UFL2 conjugates were prepared by physical, chemical, and microwave methods with the aim of using the conjugates as tablet superdisintegrant. Various powder tests, namely, angle of repose, bulk density, tapped density, Hausner’s ratio, Carr’s index, swelling index, and powder porosity were conducted on the samples. The conjugates were characterized by ATR-FTIR, XRD, DSC, and SEM techniques. Heckel and Kawakita models were applied to carry out compression studies for the prepared conjugates. Fast disintegrating tablets of domperidone were prepared using corn starch and corn Starch-Neusilin UFL2 conjugates as tablet superdisintegrants in different concentrations. Conjugates were found to possess good powder flow and tabletting properties. Heckel analysis indicated that the conjugates prepared by microwave method showed the slowest onset of plastic deformation while Kawakita analysis indicated that the conjugates prepared by microwave method exhibited the highest amount of total plastic deformation. The study revealed that the corn Starch-Neusilin UFL2 conjugates possess improved powder flow properties and could be a promising superdisintegrant for preparing fast disintegrating tablet. Also, the results sugessted that the microwave method was found to be most effective for the preparation of corn Starch-Neusilin UFL2 conjugates. Prateek Juneja, Birender Kaur, Oluwatoyin A. Odeku, and Inderbir Singh Copyright © 2014 Prateek Juneja et al. All rights reserved. Application of Experimental Design in Preparation of Nanoliposomes Containing Hyaluronidase Tue, 09 Sep 2014 08:02:43 +0000 Hyaluronidase is an enzyme that catalyzes breakdown of hyaluronic acid. This property is utilized for hypodermoclysis and for treating extravasation injury. Hyaluronidase is further studied for possible application as an adjuvant for increasing the efficacy of other drugs. Development of suitable carrier system for hyaluronidase would help in coadministration of other drugs. In the present study, the hyaluronidase was encapsulated in liposomes. The effect of variables, namely, phosphatidylcholine (PC), cholesterol, temperature during film formation (T1), and speed of rotation of the flask during film formation (SPR) on percentage of protein encapsulation, was first analyzed using factorial design. The study showed that level of phosphatidylcholine had the maximum effect on the outcome. The effect of interaction of PC and SPR required for preparation of nanoliposomes was identified by central composite design (CCD). The dependent variables were percentage protein encapsulation, particle size, and zeta potential. The study showed that ideal conditions for production of hyaluronidase loaded nanoliposomes are PC—140 mg and cholesterol 1/5th of PC when the SPR is 150 rpm and T1 is 50°C. Narayanan Kasinathan, Subrahmanyam​ Mallikarjuna Volety​, and Venkata Rao Josyula​ Copyright © 2014 Narayanan Kasinathan et al. All rights reserved. Hydroxypropyl-β-cyclodextrin: A Novel Transungual Permeation Enhancer for Development of Topical Drug Delivery System for Onychomycosis Wed, 06 Aug 2014 07:24:38 +0000 The treatment of onychomycosis is a challenging task because of unique barrier properties of the nail plate which hampers the passage of antifungal drugs in a concentration required to eradicate the deeply seated causative fungi in the nail bed. In present investigation, application of hydroxypropyl-β-cyclodextrin (HP-β-CD) was established as an effective and nail friendly transungual drug permeation enhancer especially for poorly water soluble drugs using terbinafine hydrochloride as a poorly soluble drug. HP-β-CD significantly improves hydration of nail plates and increases solubility of terbinafine hydrochloride in the aqueous environment available therein, which leads to uninterrupted drug permeation through water filled pores of hydrogel-like structure of hydrated nail plates. A nail lacquer formulation was designed with an objective to deliver the drug in an effective concentration across nail plates, using HP-β-CD as a permeation enhancer. The formulations containing HP-β-CD showed higher flux than the control formulation in in vitro drug permeation study. The formulation containing 10% w/v of HP-β-CD showed maximum flux of  μg/mL/cm2 as compared to the control flux of  μg/mL/cm2. This finding supports application of HP-β-CD as an effective permeation enhancer for transungual delivery of terbinafine hydrochloride and possibly other poorly water soluble drugs where HP-β-CD can act as a solubilizer. Pradeep Chouhan and T. R. Saini Copyright © 2014 Pradeep Chouhan and T. R. Saini. All rights reserved. Tailor-Made Pentablock Copolymer Based Formulation for Sustained Ocular Delivery of Protein Therapeutics Sun, 22 Jun 2014 06:08:27 +0000 The objective of this research article is to report the synthesis and evaluation of novel pentablock copolymers for controlled delivery of macromolecules in the treatment of posterior segment diseases. Novel biodegradable PB copolymers were synthesized by sequential ring-opening polymerization. Various ratios and molecular weights of each block (polyglycolic acid, polyethylene glycol, polylactic acid, and polycaprolactone) were selected for synthesis and to optimize release profile of FITC-BSA, IgG, and bevacizumab from nanoparticles (NPs) and thermosensitive gel. NPs were characterized for particle size, polydispersity, entrapment efficiency, and drug loading. In vitro release study of proteins from NPs alone and composite formulation (NPs suspended in thermosensitive gel) was performed. Composite formulations demonstrated no or negligible burst release with continuous near zero-order release in contrast to NPs alone. Hydrodynamic diameter of protein therapeutics and hydrophobicity of PB copolymer exhibited significant effect on entrapment efficiency and in vitro release profile. CD spectroscopy confirmed retention of structural conformation of released protein. Biological activity of released bevacizumab was confirmed by in vitro cell proliferation and cell migration assays. It can be concluded that novel PB polymers can serve a platform for sustained delivery of therapeutic proteins. Sulabh P. Patel, Ravi Vaishya, Gyan Prakash Mishra, Viral Tamboli, Dhananjay Pal, and Ashim K. Mitra Copyright © 2014 Sulabh P. Patel et al. All rights reserved. Mucoadhesive Hydrogel Films of Econazole Nitrate: Formulation and Optimization Using Factorial Design Tue, 10 Jun 2014 05:14:15 +0000 The mucoadhesive hydrogel film was prepared and optimized for the purpose of local drug delivery to oral cavity for the treatment of oral Candidiasis. The mucoadhesive hydrogel film was prepared with the poly(vinyl alcohol) by freeze/thaw crosslinking technique. 32 full factorial design was employed to optimize the formulation. Number of freeze/thaw cycles (4, 6, and 8 cycles) and the concentration of the poly(vinyl alcohol) (10, 15, and 20%) were used as the independent variables whereas time required for 50% drug release, cumulative percent of drug release at 8th hour, and “” of zero order equation were used as the dependent variables. The films were evaluated for mucoadhesive strength, in vitro residence time, swelling study, in vitro drug release, and effectiveness against Candida albicans. The concentration of poly(vinyl alcohol) and the number of freeze/thaw cycles both decrease the drug release rate. Mucoadhesive hydrogel film with 15% poly(vinyl alcohol) and 7 freeze/thaw cycles was optimized. The optimized batch exhibited the sustained release of drug and the antifungal studies revealed that the drug released from the film could inhibit the growth of Candida albicans for 12 hours. Balaram Gajra, Saurabh S. Pandya, Sanjay Singh, and Haribhai A. Rabari Copyright © 2014 Balaram Gajra et al. All rights reserved. Interpenetrating Polymer Networks as Innovative Drug Delivery Systems Wed, 14 May 2014 09:19:28 +0000 Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs) have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs. Alka Lohani, Garima Singh, Shiv Sankar Bhattacharya, and Anurag Verma Copyright © 2014 Alka Lohani et al. All rights reserved. Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha-Cyclodextrin with Model Membranes by 1H-, 2H-, 31P-NMR and Electron Spin Resonance Mon, 05 May 2014 11:15:00 +0000 The properties of an amorphous solid dispersion of cyclosporine A (ASD) prepared with the copolymer alpha cyclodextrin (POLYA) and cyclosporine A (CYSP) were investigated by 1H-NMR in solution and its membrane interactions were studied by 1H-NMR in small unilamellar vesicles and by 31P 2H NMR in phospholipidic dispersions of DMPC (dimyristoylphosphatidylcholine) in comparison with those of POLYA and CYSP alone. 1H-NMR chemical shift variations showed that CYSP really interacts with POLYA, with possible adduct formation, dispersion in the solid matrix of the POLYA, and also complex formation. A coarse approach to the latter mechanism was tested using the continuous variations method, indicating an apparent 1 : 1 stoichiometry. Calculations gave an apparent association constant of log Ka = 4.5. A study of the interactions with phospholipidic dispersions of DMPC showed that only limited interactions occurred at the polar head group level (31P). Conversely, by comparison with the expected chain rigidification induced by CYSP, POLYA induced an increase in the fluidity of the layer while ASD formation led to these effects almost being overcome at 298 K. At higher temperature, while the effect of CYSP seems to vanish, a resulting global increase in chain fluidity was found in the presence of ASD. Jean-Claude Debouzy, David Crouzier, Fréderic Bourbon, Malika Lahiani-Skiba, and Mohamed Skiba Copyright © 2014 Jean-Claude Debouzy et al. All rights reserved. Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells Thu, 24 Apr 2014 08:19:00 +0000 During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. Vaibhav Rastogi, Pragya Yadav, Shiv Sankar Bhattacharya, Arun Kumar Mishra, Navneet Verma, Anurag Verma, and Jayanta Kumar Pandit Copyright © 2014 Vaibhav Rastogi et al. All rights reserved.