Current Drug Delivery (v.11, #3)

Nanosuspensions as a Versatile Carrier based Drug Delivery System - An Overview by Beeravelli Sudhakar, Kothagunda NagaJyothi, K.V. Ramana Murthy (299-305).
Nanotechnology is being explored in many ways to design a new chemical entity (NCE) to an active pharmaceuticalingredient (API). Of the different nanotechnologies, Nanosuspensions has gained a lot of interest due to its ease ofproduction and applicability to a large number of drugs. This present review article on nanosuspensions is focused on thevarious principles, production techniques, stability problems, various marketed formulations and current trends associatedwith the nanosuspensions.

Helicobacter pylori: An Overview on Antimicrobials and Drug Delivery Systems for its Eradication by Sally A. El-Zahaby, Abeer A. Kassem, Amal H. El-Kamel (306-312).
Since the discovery of Helicobacter pylori (H. pylori) in the early 1980s, its eradication has been one of themost important global challenges in gastroenterology. Various circumstances make the treatment with antimicrobials particularlydifficult. One problem has been that antibiotics commonly used were designed for the treatment of infectionsthroughout the body rather than for delivering high concentrations locally within the stomach. Many gastroretentive dosageforms were developed in order to eradicate the infection, yet additional advancements are still needed to eliminate theinfection completely and decrease its prevalence worldwide. An overview on different antimicrobials and a literature surveyabout different drug delivery systems used in eradication of H. pylori infection are presented in this review.

The work investigates the formulation and evaluation of microemulsions containing olive oil, Tween 80 andisopropyl alcohol for transdermal candesartan cilexetil delivery. The pseudoternary phase diagram was constructed to determinecomposition of microemulsions. These formulated microemulsions were evaluated for in vitro skin permeationand stability. The microemulsion containing 72 % olive oil, 8 % water, 15 % Tween 80, and 5 % isopropylalcohol showedmaximum viscosity of 29.54±0.32 mPas, average small droplet size of 180.90 nm, smaller polydispersity index of 0.37,zeta potential of -12.20 and maximum candesartan cilexetil permeation flux of 0.49±0.05 ?g/cm2/h through excised porcineskin. The degradation of candesartan cilexetil microemulsions after 3 months storage was found low and its shelf-lifewas calculated as 3.92 years at room temperature.

Mucoadhesive Microspheres Containing Anti-Hypertensive Agent: Formulation and Characterization by Ankita Sunilbhai Patel, Pande Saikat, Patel Ronakkumar Pravinbhai (322-331).
The spherical microspheres consisting of Furosemide loaded sodium alginate and along with HPMC E50 or sodiumCMC as mucoadhesive polymers in different ratios were prepared using ionic gelation technique. Calcium chloridewas used as crosslinking, to retard the drug release from the mucoadhesive microspheres. The prepared mucoadhesive microsphereswere subjected for evaluation of various parameters like production yield, particle size, encapsulation efficiency,mucoadhesion test and in vitro dissolution profile studies. Formulations were subjected to DSC study and SEManalysis. The in vitro release data were well fit into Higuchi and Korsmeyer-Peppas model and followed non-Fickian diffusionmechanism.

In the present study, ethosomal and liposomal formulations containing tamoxifen citrate were prepared andevaluated for their penetration properties in human cadaver skin using Franz diffusion cell and confocal laser scanningmicroscope (CLSM). The results clearly revealed that ethosomal vesicles showed a better drug permeation profile thanthat of liposomal vesicles. In addition, low fluorescence intensity in CLSM was recorded with liposomes as compared toethosomes, indicating lower cumulative amount of drug permeation from liposomal vesicles. Furthermore, CLSM showeduniform fluorescence intensity across the entire depth of skin in ethosomal treatment, indicating high penetrability ofethosomal vesicles through human cadaver skin. In contrast, low penetrability of conventional liposomal vesicles was recordedas penetration was limited to the 7th section (i.e. upper epidermis layer) of skin as evident from visualization of intactliposomal vesicles in CLSM.

Novel Oral Suspensions: A Review by Harsha Kathpalia, Chetan Phadke (338-358).
An oral pharmaceutical suspension has been one of the most favorable dosage forms for pediatric and geriatricpatients or patients unable to tolerate solid dosage forms. The liquid form is preferred because of the ease of swallowingand flexibility in the administration of doses. This emerging area of suspensions as applied to the pharmaceutical field arediscussed in the current article enlightening the vision of the readers towards pharmaceutical formulations including nanosuspensions,non-aqueous suspensions and modified release suspensions. The emphasis in the article focuses on the essentialprinciples involved in the process of formation of different types of suspensions and their applications, since noveloral suspensions have potential to provide various strategy systems.

Preparation and Characterization of Rivastigmine Loaded Human Serum Albumin (HSA) Nanoparticles by Amelia M. Avachat, Yogesh M. Oswal, Kishor N. Gujar, Rohit D. Shah (359-370).
The aim of the present study was to develop and characterize rivastigmine loaded Human Serum Albumin(HSA) nanoparticles (NPs) for sustained release. Rivastigmine tartrate (RT) is a short acting cholinesterase inhibitor(ChEI) used for Alzheimer's disease (AD). In the present study sustained release nanoparticulate formulation of RT wasprepared, optimized (using 32 factorial design) and characterized (using biodegradable polymer HSA as a carrier). HSANPs were prepared by desolvation-crosslinking technique using ethanol with variable drug/polymer ratios (1:1, 1:2, 1:3,and 1:5) and using glutaraldehyde as a crosslinking agent. All prepared nanoparticles were coated with polysorbate-80 tofacilitate brain targeting via endocytosis. Effect of key formulation variables on particle size (PS) and percentage drug entrapment(PDE) of NPs was studied by using 32 factorial design. Among different ratios studied, 1:2 showed minimum PSof 83.71 ± 4.2 nm with highest PDE of 81.46 ± 0.76 %. FTIR interpretation showed that there is no interaction betweenthe drug and excipients used, DSC thermograms indicated that RT was dispersed as an amorphous state in HSA NPs.SEM studies indicated that the drug was completely entrapped in HSA NPs. In vitro studies showed 55.59 ± 3.80% releaseof drug from HSA NPs in 12 h. The experimental results showed the suitability of HSA nanoparticles as a potentialcarrier for providing sustained delivery of RT.

A Gastroretentive Drug Delivery System of Lisinopril Imbibed on Isabgol- Husk by Ravindra Semwal, Ruchi Badoni Semwal, Deepak Kumar Semwal (371-379).
The gastroretentive drug delivery system is site-specific and allows the drug to remain in the stomach for aprolonged period of time so that it can be released in a controlled manner in gastrointestinal tract. The present study wascarried out to develop a gastroretentive drug delivery system using isabgol as an excipient to prolong the residence time ofthe model drug lisinopril in the stomach. The gastroretentive ability of isabgol was increased by addition of NaHCO3 as agas-generating agent while its mucoadhesive property was enhanced by incorporation of HPMC-K4M. The drug, NaHCO3and HPMC-K3M were imbibed on isabgol-husk as per entrapment efficiency of the isabgol-husk. After drying, the productwas filled in a hard gelatin capsule and evaluated for its buoyancy, mucoadhesive properties, swelling index and in vitrodrug release. The lisinopril released through isabgol was delayed by 12 hours when compared to a preparation availableon the market which released the complete drug in 0.5 hours. The drug release study of lisinopril from the formulationfollows first order kinetics using a diffusion controlled mechanism. The results from the present study revealed thatisabgol can be used as a potential excipient for the formulation of gastroretentive drug delivery systems in the near future.

Optimization of Aceclofenac Solid Dispersion Using Box-Behnken Design: in-vitro and in-vivo Evaluation by Furqan A. Maulvi, Vaishali T. Thakkar, Tejal G. Soni, Tejal R. Gandhi (380-391).
The study investigates the combined influence of three independent variables in preparation of aceclofenac ternarysolid dispersion (SD) by kneading method. A 3-factor, 3-level Box-Behnken design was used. Independent variablesselected were microcrystalline cellulose (Avicel 200 = X1), hydroxypropyl methylcellulose-5 cps (HPMC E-5 = X2), andratio of drug to polymer mixture (X3). Fifteen batches were prepared and evaluated for angle of repose and percentagedrug release at 5 minutes (Q5). The transformed values of variables were subjected to multiple regression analysis to establisha second-order polynomial equation. Contour plots were constructed to evaluate the effects of X1, X2 and X3 on Q5and angle of repose. Model was validated for accurate prediction of Q5 and angle of repose (AR) by performing checkpointanalysis. The computer optimization process and contour plots predict the levels of independent variables as X1=+0.5, X2 = -1 and X3 = +0.35 for maximized response of Q5 with better flow property. The stability study during 6 monthsconfirms that aceclofenac exhibits high stability in solid dispersion. In vivo studies indicate that optimized ternary soliddispersion provides rapid pharmacological responses in mice and rats compared to marketed formulation.

Floating pulsatile is combined approach designed according to circadian rhythm to deliver the drug at righttime, in right quantity and at right site as per pathophysiological need of disease with prolong gastric residence and lagphase followed by burst release. As the migraine follows circadian rhythm in which headache is more painful at the awakeningtime, the dosage form should be given during night time to release drug when pain get worsen. Present work dealswith formulation and optimization of floating pulsatile tablet of sumatriptan succinate. Core tablet containing crospovidoneas superdisintegrant (10%) showed burst release. Lag time was maintained using swellable polymer as polyoxN12Kand xanthum gum. 32 experimental design was carried out. Developed formulations were evaluated for physical characteristics,in vitro and in vivo study. Optimized batch F2 with concentration of polyox N12K (73.43%) and xanthum gum(26.56%) of total polymer weight showed floating lag time 15±2 sec, drug content 99.58±0.2 %, hardness 6±0.2 Kg/cm2and drug release 99.54±2% with pulsatile manner followed lag period of 7±0.1h. In vivo x-ray study confirms prolonggastric residence of system. Programmable pulsatile release has been achieved by formulation F2 which meet demand ofchronotherapeutic objective of migraine.

5-Fluorouracil (5-FU) is one of the most effective antineoplastic agents used for the treatment of skin cancersand actinic keratosis (AK). Currently commercial formulation for topical 5-FU administration is available in the form ofsolution or cream. Commercial topical formulations are associated with the limitation of very short retention time at theadministration site resulting in very poor skin permeation and deposition of drug. In the present study attempt was madefor the preparation, optimization and characterization of bioadhesive gel formulations for localized delivery of 5-FU. Fourbioadhesive gel formers, Carbopol 934, Carbopol 980, Methylcellulose (MC) and Poloxamer 188 were selected for thepreparation of 5-FU bioadhesive gel formulations. The formulations were characterized for characteristic parameters includingbioadhesive strength, skin deposition and interaction study. Carbopol 934 based bioadhesive gel formulation atthe concentration of 1.5% w/w showed the best physicochemical properties such as viscosity (2670±12.2 cP), which wassimilar to the value obtained with the marketed cream (2870±14.4 cP), highest skin deposition (1290±56.4?g) and bioadhesivestrength (18.62 gf). Cutaneous irritation of optimized bioadhesive gel formulations was also tested using the Draizetest and only very slight erythema and no oedema was observed. In comparison, marketed formulation showed well definederythema along with oedema formation. The result of the present study demonstrated that formulation of Carbopol934 based 5-FU bioadhesive gel is a better alternative to the traditional cream base for enhanced topical delivery of 5-FU.The developed formulation will have the ease of application, better skin deposition and sustained release characteristicwith reduced skin toxicity.

Oral mucositis is one of the major side effects of cancer chemotherapy (30-76%) and radiotherapy (over 50%).Current palliative treatments of oral mucositis include specialized agents like pelifermin, platelet derived factors etc. ororal hygienic agents which suffered from various drawbacks like systemic side effect, least effect owing to fast wash outof buccal mucosa, patient unfriendly delivery systems, and mere symptomatic relief. In this research work, N-succinylchitosan gel delivery system of microemulsified eugenol, honey and sodium hyaluronate was prepared to explore theirmultiple and synergistic effects on various pathological factors of oral mucositis. N-succinyl chitosan was synthesized inour laboratory and loaded with microemulsified eugenol (10% v/v), honey (10% v/v) and sodium hyaluronate (0.2% w/v)to prepare orogel with optimum pH, spreadability, mucoadhesion strength, and viscosity. In vitro eugenol release fromN-succinyl chitosan gel after 8 hours in PBS (pH-6.4) was found to be 87.45±0.14%, which was better in comparison tothat released from chitosan gel. Ex vivo penetration studies using rat buccal mucosal tissue also suggested better J-effluxof eugenol through N-succinyl chitosan in comparison to chitosan gel with enhancement ratio (ER) of 1.71. The antimicrobialeffect of N-succinyl chitosan based orogel against S. aureus and C. albicans efficacy was found to be statistically highin comparison to chitosan based orogel as well as marketed formulation of chlorhexidine (p<0.05). The N-succinyl chitosanorogel in 5-fluoro uracil induced oral mucositis animal (Wistar rats) model showed enhanced survival ratio, weight gain andhigh tissue regeneration activity than chitosan gel formulation within 15 days. The formulation was successful in elevatingthe survival and reducing the inflammation in the oral mucosa of animals compared to disease control (p<0.05) and hencesuggesting the potential of N-succinyl chitosan orogel in the treatment of oral mucositis.