Current Drug Delivery - Volume 10, Issue 3, 2013

An oromucosal mucoadhesive suspension (OMS) able to combine the peculiarities of prolonged release mucoadhesive microparticles with those of an immediate release oromucosal solution is described. Microparticles were obtained by ionotropic gelation of alginate blended with another mucoadhesive material in a one step process where the cross-linking bath constituted the suspension vehicle. The effects of formulation and processing conditions on OMS performances were measured in-vitro determining the enhancement of drug penetration in buccal porcine mucosa and inhibition of tooth plaque formation using flurbiprofen and delmopinol as model drugs, respectively. Well-formed and spherical microparticles were obtained combining alginate with carbomer; linear dependence of particle size from the feed composition, viscosity and atomization pressure was found. As demonstrated by using FITC-labelled microparticles, the system remained onto the buccal mucosa at least for a six hour period. As a consequence, 0.1% flurbiprofen OMS guaranteed a concentration of flurbiprofen into buccal porcine mucosa over 6 hours comparable to 0.25% flurbiprofen reference solution, allowing a potential reduction of the 60% administered dose. The use of in-house made artificial mouth revealed that the once-a-day administration of 0.1% delmopinol OMS was as effective in plaque inhibition as the 0.2% delmopinol reference solution product given twice-a-day. These results suggested that the development of bioadhesive oromucosal suspensions, localizing the drug into buccal cavity, can reduce regimen and administrated dose.

There is a growing interest in the use of anticariogenic and antimicrobial agents to prevent demineralization and promote remineralization of dental enamel for the prevention of oral diseases. The purpose of this study was to develop a novel chewing-system containing as Casein-Phosphopeptides-Amorphous-Calcium-Phosphate (CPP-ACP) as Quercetin (Qt) and evaluate their release using in vitro and in vivo experiments. In vitro and in vivo experimental protocols were designed to test the percentages of Ca from CPP-ACP and Qt released with time and their delivery rate from a chewing gum. The in vitro experiments were performed using a specifically designed chewing apparatus to test the release of Ca and Qt in artificial saliva in function of chewed time, while the in vivo experiments required a chew-out method with volunteers and the residual CPP-ACP and Qt present in the chewed gums was analyzed. This study demonstrated that both CPP-ACP'Ca and Qt were released during chewing although CPP-ACP'Ca was released from the chewing gum in a slower and more controlled manner than Qt. They were also both effectively retained in the oral cavity for all the investigated chewing time and according to their monitored release concentrations they were able to serve as a novel antiplaque agent. This research concludes that both drugs were efficiently released during the mastication process to fully exploit their anti-carious activity.

This present study compares the efficacy of microsphere formulations, and their method of antigen presentation, for the delivery of the TB sub-unit vaccine antigen, Ag85B-ESAT-6. Microspheres based on poly(lactide-coglycolide) (PLGA) and chitosan incorporating dimethyldioctadecylammonium bromide (DDA) were prepared by either the w/o/w double emulsion method (entrapped antigen) or the o/w single emulsion method (surface bound antigen), and characterised for their physico-chemical properties and their ability to promote an immune response to Ag85B-ESAT-6. The method of preparation, and hence method of antigen association, had a pronounced effect on the type of immune response achieved from the microsphere formulations, with surface bound antigen favouring a humoural response, whereas entrapped antigen favoured a cellular response.

In the present work a series of imprinted (MIPs) and non-imprinted (NIPs) hydrogels were prepared using 2-hydroxyethyl methacrylate (HEMA) as a backbone monomer, ethylene glycol dimethacrylate (EGDMA) as a cross-linker monomer, methacrylic acid (MAA) as a functional monomer and dorzolamide (DZD) as the template molecule. Different concentrations of MAA (0, 100, 200, 400 mM) were used for preparation of NIPs. Two DZD: MAA molar ratios (1:8 and 1:4) and 400 mM MAA were also applied in imprinting process. The hydrogels (0.4 mm thickness) were synthesized by thermal polymerization at 50°C in 24h in a polypropylene mould. Then, the swelling and binding properties of hydrogels were evaluated in water. Their loading and releasing properties were also studied in NaCl 0.9% and artificial lachrymal fluid. The results showed that using MAA as co-monomer and applying molecular imprinting technique increased loading capacity of hydrogels. The optimized imprinted hydrogel (MIP1:4), prepared with 400 mM MAA and DZD: MAA molar ratio of 1:4, had the highest affinity for DZD and the greatest ability to control the release process in aqueous media. Our data indicated that the use of suitable co-monomer and applying a molecular imprinting technique had important influence on loading and releasing properties of hydrogels.

Gastric floating drug delivery systems have been an avenue of considerable interest in terms of their immense potential for better pharmacotherapeutic interventions along with site-specific absorption. These buoyant systems significantly enhance the bioavailability and controlled delivery of several drug molecules. Scientific investigators have also carried out substantial research endeavours worldwide in order to design a more systematic and intellectual floating systems. The present manuscript is an attempt to highlight numerous recent advancements in the design of gastric floating drug delivery systems along with various available commercial preparations. Salient applications, characterization aspects and future perspectives of these multifarious systems have also been addressed.

The aim of the present work was to develop colon specific drug delivery system for ibuprofen using natural polymers as carriers. We have investigated colon specific, pulsatile device to achieve time and site specific release of ibuprofen based on chronopharmaceutical considerations. The basic design consists of an insoluble hard gelatin capsule body, filled with ibuprofen surface solid dispersions and sealed with guar gum hydrogel plug. The entire capsule was coated with ethyl cellulose, so that the variability in gastric emptying time can be overcome and a colon specific release can be achieved. Surface solid dispersions (SSDs) of ibuprofen were prepared using natural polymers such as Guar gum (GG), Hupu gum (HG) and Xanthan gum (XG) in the weight ratios of 1:0.5, 1:1 and 1:2 by using solvent evaporation method. Physicochemical properties of the prepared SSD were characterized by FTIR and DSC. Optimized SSD were obtained by practical yield, drug content, solubility and dissolution studies and were selected for further fabrication of pulsincaps. Guar gum was used as hydrogel plug material to maintain a suitable lag period. The prepared pulsincaps were evaluated for in-vitro release. Pulsincap formulated with Ibuprofen-Hupu gum (PF3) at 1:2 ratio of surface solid dispersions showed highest drug release over the period of 12 hr and release was found to be Higuchi model kinetics. The present research study results have confirmed that the modified pulsincap of ibuprofen is a suitable device for the time dependent and site specific delivery to the colon segment of GIT.

Dapivirine, formerly known as TMC 120, is a poorly-water soluble anti-HIV drug, currently being developed as a vaginal microbicide. The clinical use of this drug has been limited due to its poor solubility. The aim of this study was to design solid dispersion systems of Dapivirine to improve its solubility. Solid dispersions were prepared by solvent and fusion methods. Dapivirine release from the solid dispersion system was determined by conducting in-vitro dissolution studies. The physicochemical characteristics of the drug and its formulation were studied using Differential Scanning Calorimetry (DSC), powder X-ray Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). A significant improvement in drug dissolution rate was observed with the solid dispersion systems. XRD, SEM and DSC results indicated the transformation of pure Dapivirine which exists in crystalline form into an amorphous form in selected solid dispersion formulations. FTIR and HPLC analysis confirmed the absence of drugexcipient interactions. Solid dispersion systems can be used to improve the dissolution rate of Dapivirine. This improvement could be attributed to the reduction or absence of drug crystallinity, existence of drug particles in an amorphous form and improved wettability of the drug.

The mucoadhesive microparticles (CHCNZ) composed of chitosan (CH) and cinnarizine (CNZ) hydrochloride were successfully prepared, in a process of solution-enhanced dispersion, by supercritical CO2 (SEDS) technique. Scanning electron microscopy was used to reveal the morphological characteristics of mucoadhesive microparticles. The average particle size of microparticles was in the range from 1.9 to 12.8 µm. In vitro and in vivo mucoadhesive tests showed that CHCNZ mucoadhesive microparticles adhered more strongly to gastric mucous layer. Thereby retaining in gastrointestinal tract for an extended period of time and exhibiting good mucoadhesive properties. The X-ray powder diffractometry and differential scanning calorimetry analysis demonstrated that the SEDS process was an efficient physical coating process to produce CHCNZ composite microparticles. It also suggests that CNZ did not undergo chemical changes during the production of microparticles. The optimized batch exhibited a high drug entrapment efficiency of 67 % with particle size of 3.9 µm. A sustained pattern of drug release was obtained for more than 20 h. In vivo studies were carried out by administering orally cinnarizine HCl (CNZ) suspension and mucoadhesive microparticles to rabbits under fasted (for 12 h) conditions. The results showed that CNZ mucoadhesive microparticles had a better bioavailability than CNZ suspension due to longer retention in the gastric environment of the test animals.

Ovarian cancer is the ninth most common cancer amongst women and ranked as fifth in terms of the cause of cancer related mortality accounting for more deaths than any other cancer of the female reproductive system. Gemcitabine is the most common chemotherapeutic agent used in the treatment of ovarian cancer despite of its disadvantage of having a very lesser half life. In this study, we have envisaged the use of a highly porous, biomimetic and implantable pectin scaffold embedded with gemcitabine loaded fibrin nanoconstructs to improve the half life of the drug, thereby providing localized therapy for ovarian cancer. The controlled and sustained release of the chemokine from the scaffold system was extensively analyzed in vitro different pH environments. The composite scaffolds were found to be highly biocompatible when tested with mammalian cell lines. The excellent cytotoxicity and apoptosis responses induced in ovarian cancer, PA- 1 cell lines proved that the nanocomposite Pectin scaffolds loaded with specific chemokine can be used as implantable “therapeutic wafers” for distracting metastatic cancer cells and thus improve the survival rate of ovarian cancer afflicted individuals.

psyllium, a medicinally active gel forming natural polysaccharide and a dietary fiber has been used as a medicine in myriad of conditions such as constipation and inflammatory bowel syndrome. One of its more recent uses that have received attention has been its ability to reduce blood sugar levels in diabetics. Therefore present work is an attempt to formulate anti diabetic drug Metformin as a controlled release floating delivery making use of pysllium as release retardant and to assist the drug in stabilizing blood sugar level in type II diabetics. Drug and excipients compatibility studies were monitored by thermal analysis using differential scanning calorimeter (DSC) and Fourier transform infra red (FTIR). The DSC thermogram and FTIR of drug and drug-polymer mixture did not reveal any incompatibility. psyllium was tried in different concentrations along with other polymers like HPMC K15M and carbopol 940 to achieve the desired release profile. The total drug: polymer ratio was kept between 1:0.4 to 1:0.5, and different polymer combinations were tried to achieve desired drug release for 12 hours. The prepared tablets were evaluated for in vitro release studies and floating behavior. Our conclusion from the present study indicated that pysllium could potentially be used in conjunction with other polymers to formulate controlled release formulations of anti-diabetic drugs to provide better control over blood glucose levels.

Summary: Vertigo has a negative impact on quality of life; therefore, it is important to find an effective and convenient therapy that allows patients to continue their everyday tasks as soon as possible and to have a better quality of life. Methods: There were two formulations used to assess the effectiveness in vertigo treatment from peripheral origin: nimodipine administrated three times daily (Nimotop®) 30 mg versus nimodipine AP administrated once daily (Tropocer ®) 90 mg; both of them in a administrated in a prospective, randomized, double-blind, double dummy, multicenter and parallel-group study, where patients with peripheral vertigo defined as a score ≥7 on the Vertigo-Dizziness Differential Diagnosis Score were included. The patients were evaluated by vertigo severity index and vestibular disability index. Results: In the AP nimodipine group (NAP), vertigo severity index was decreased by 50%: 24% of patients in 14 days, 41% in 4 weeks and 89% in 8 weeks. The vestibular disability index was decreased by 50%: 24% of patients in 15 days, 83% in 4 weeks and 92% of patients in 8 weeks. In the conventional nimodipine group (NC), rate of vertigo severity was decreased by 50%: 17% of patients in 14 days, 41% of patients in 4 weeks and 90% of patients in 8 weeks. The vestibular disability index was decreased by 50%: 15 days in 17% of patients, 53% in 4 weeks and 64% in 8 weeks, without difference between groups. Conclusions: both products were effective and well tolerated in the treatment of peripheral vertigo.

Chitosan is a polymer derived from chitin that is widely available at relatively low cost, but due to compression challenges it has limited application for the production of direct compression tablets. The aim of this study was to use certain process and formulation variables to improve manufacturing of tablets containing chitosan as bulking agent. Chitosan particle size and flow properties were determined, which included bulk density, tapped density, compressibility and moisture uptake. The effect of process variables (i.e. compression force, punch depth, percentage compaction in a novel double fill compression process) and formulation variables (i.e. type of glidant, citric acid, pectin, coating with Eudragit S®) on chitosan tablet performance (i.e. mass variation, tensile strength, dissolution) was investigated. Moisture content of the chitosan powder, particle size and the inclusion of glidants had a pronounced effect on its flow ability. Varying the percentage compaction during the first cycle of a double fill compression process produced chitosan tablets with more acceptable tensile strength and dissolution rate properties. The inclusion of citric acid and pectin into the formulation significantly decreased the dissolution rate of isoniazid from the tablets due to gel formation. Direct compression of chitosan powder into tablets can be significantly improved by the investigated process and formulation variables as well as applying a double fill compression process.

With over 10 million new cases per year worldwide, Cancer remains one of the most urgent health concerns and a difficult disease to treat. For an effective treatment, improved diagnostic and therapeutic techniques with minimal side-effects are required. Research and development in the areas of nanoscience and nanotechnology promise to provide innovative and more effective approaches for early diagnosis, imaging and therapy. An emerging trend in this direction is Theranostics which represents a combinatorial diagnosis and therapeutic approach to cancer disease and aims to eliminate multi-step procedures, reduce delays in treatment and improves patient care. It offers various advantages like improved diagnosis, tumor specific delivery of drugs, reduced lethal effects to normal tissues etc. Theranostic nanomedicines like nanoshells, plasmonic nanobubbles, quantum dots etc. can be used effectively for achieving these goals. With the advances in nano-imaging and nano-therapy new avenues for the development of effective cancer treatment will be opened.