Pravin Pawar

Orally dissolving strips: A new approach to oral drug delivery system

Recently, fast dissolving films are gaining interest as an alternative of fast dissolving tablets. The films are designed to dissolve upon contact with a wet surface, such as the tongue, within a few seconds, meaning the consumer can take the product without need for additional liquid. This convenience provides both a marketing advantage and increased patient compliance. As the drug is directly absorbed into systemic circulation, degradation in gastrointestinal tract and first pass effect can be avoided. These points make this formulation most popular and acceptable among pediatric and geriatric patients and patients with fear of choking. Over-the-counter films for pain management and motion sickness are commercialized in the US markets. Many companies are utilizing transdermal drug delivery technology to develop thin film formats. In the present review, recent advancements regarding fast dissolving buccal film formulation and their evaluation parameters are compiled.

Ocular drug delivery system: a reference to natural polymers

Introduction: Ocular drug delivery is a very challenging endeavor due to the unique anatomical and physiological barriers. The low ocular bioavailability (<10%) obtained from conventional formulations has forced the scientists to develop new formulations to deliver drugs to ocular tissues at a controlled rate to reduce frequent instillations. The natural polymers have represented the potential to deliver drugs topically through the limited precorneal area and release over a prolonged time period. Areas covered: The important points to be considered during the fabrication of ophthalmic formulations for example, properties of drug molecule and polymer which affect the release rate are discussed. Novel polymers, like arabinogalactan, xyloglucan, gum cordia, locust bean gum, carrageenan and Bletilla striata polysaccharide, besides the conventional polymers like chitosan, starch, sodium alginate, sodium hyaluronate, xanthan gum, gelatin, gellan gum, guar gum, collagen and albumin, have demonstrated the potential to safely deliver drugs at a controlled rate in different ophthalmic formulations. Expert opinion: The limitations of topical delivery of genes and chemotherapeutic drugs can be overcome by using natural polymers with characteristic properties. Despite the wide applicability, tremendous efforts are required to establish natural polymers in novel formulations on a commercial scale.

Metformin loaded non-ionic surfactant vesicles: optimization of formulation, effect of process variables and characterization

BackgroundMetformin an oral hypoglycemic has been widely used as a fist line of treatment of Type II Diabetes but in a very high dose 2–3 times a day and moreover suffers from a number of side effects like lactic acidosis, gastric discomfort, chest pain, allergic reactions being some of them. The present work was conducted with the aim of sustaining the release of metformin so as to decrease its side effects and also reduce its dosing frequency using a novel delivery system niosomes (non-ionic surfactant vesicles). Non-ionic surfactant vesicles of different surfactants were prepared using thin film hydration technique and were investigated for morphology, entrapment, in-vitro release, TEM (transmission electron microscopy) and physical stability. Optimized formulation was further studied for the effect of Surfactant concentration, DCP (Dicetyl phosphate), Surfactant: cholesterol ratio and volume of hydration. The release studies data was subjected to release kinetics models.ResultsThe prepared vesicles were uniform and spherical in size. Optimized formulation MN3 entrapped the drug with 84.50±0.184 efficiency in the vesicles of the size 487.60±2.646 and showed the most sustained release of 73.89±0.126. Also it was resulted that 100 molar concentration of cholesterol and surfactant, Presence of DCP, equimolar ratio of span 60: cholesterol and 15 ml of volume of hydration were found to be optimum for miosome preparation.ConclusionsThe present work concluded metformin loaded niosomes to be effective in sustaining the drug release leading to decreased side effects and increased patient compliance.

Formulation and in vitro evaluation of Eudragit S-100 coated naproxen matrix tablets for colon-targeted drug delivery system

The purpose of the present investigation was to prepare matrix tablets of naproxen using a hydrophobic polymer, i.e., Eudragit RLPO, RSPO, and combination of both, by wet granulation method. The tablets were further coated with different concentrations of Eudragit S-100, a pH-sensitive polymer, by dip immerse method. In vitro drug release studies of tablets were carried out in different dissolution media, i.e., 0.1 N HCl (pH 1.2), phosphate buffers pH 6.8 and 7.4, with or without rat cecal content. The swelling studies of the optimized formulation were carried out. The physicochemical parameters of all the formulations were found to be in compliance with the pharmacopoeial standards. The effect of dissolution medium on the surface of matrix tablet was determined by using Scanning Electron Microscopy technique. The stability studies of all formulations were performed as per ICH guidelines. The results demonstrated that the tablets coated with Eudragit S-100 (2% w/v) showed a sustained release of 94.67% for 24 h, but drug release increased to about 98.60% for 24 h in the presence of rat cecal content while the uncoated tablets released the drug within 5 h. With regard to release kinetics, the data were best fitted with the Higuchi model with non-Fickian drug release kinetics mechanism. The stability studies of tablets showed less degradation during accelerated and room temperature storage conditions for 6 months. The enteric-coated Eudragit S-100 coated matrix tablets of naproxen showed promising site-specific drug delivery in the colon region.

Eudragit S-100 coated sodium alginate microspheres of naproxen sodium: formulation, optimization and in vitro evaluation.

The aim of the study was to prepare site specific drug delivery of naproxen sodium using sodium alginate and Eudragit S-100 as a mucoadhesive and pH-sensitive polymer, respectively. Core microspheres of alginate were prepared by a modified emulsification method followed by cross-linking with CaCl2, which was further coated with the pH dependent polymer Eudragit S-100 (2.5 or 5 %) to prevent drug release in the upper gastrointestinal environment. Microspheres were characterized by FT-IR spectroscopy, X-ray diffraction, differential scanning calorimetry and evaluated by scanning electron microscopy, particle size analysis, drug loading efficiency, in vitro mucoadhesive time study and in vitro drug release study in different simulated gastric fluids. Stability studies of the optimized formulation were carried out for 6 months. SEM images revealed that the surface morphology was rough and smooth for core and coated microspheres, respectively. Core microspheres showed better mucoadhesion compared to coated microspheres when applied to the mucosal surface of freshly excised goat colon. The optimized batch of core microspheres and coated microspheres exhibited 98.42 ± 0.96 and 95.58 ± 0.74 % drug release, respectively. Drug release from all sodium alginate microsphere formulations followed Higuchi kinetics. Moreover, drug release from Eudragit S-100 coated microspheres followed the Korsmeyer-Peppas equation with a Fickian kinetics mechanism. Stability study suggested that the degradation rate constant of microspheres was minimal, indicating 2 years shelf life of the formulation. Cilj istraživanja bila je ciljana isporuka naproksen natrija koristeći natrijev alginat i Eudragit S-100 kao mukoadhezivne, odnosno pH-osjetljive polimere. Jezgra mikrosfera od alginata pripravljena je modificiranom metodom emulgiranja te umrežavanjem pomoću otopine CaCl2. Sljedeći korak u pripravi mikrosfera bilo je oblaganje s pH osjetljivim polimerom Eudragit S-100 (2,5 ili 5 %) čime je spriječeno oslobađanje lijeka u gornjem dijelu gastrointestinalnog trakta. Mikrosfere su okarakterizirane FT-IR spektroskopijom, difrakcijom rendgenskih zraka, diferencijalnom pretražnom kalorimetrijom i pretražnom elektronskom mikroskopijom. Nadalje, analizirana je veličina čestica, količina uklopljenog lijeka, mukoadhezivna svojstva in vitro te oslobađanje lijeka in vitro u različitim simuliranim gastričnim fluidima. Testovi stabilnosti optimiziranih pripravaka praćeni su tijekom 6 mjeseci prema smjernicama ICH. SEM snimke otkrile su da je površina jezgre mikročestica neravna, dok je površina obloženih mikrosfera glatka. Jezgre mikrosfera imale su jače izražena mukoadhezivna svojstva nego obložene mikrosfere na testovima provedenim na svježe izrezanim dijelovima debelog crijeva koze. Iz optimiziranih neobloženih i obloženih mikrosfera oslobađa se 98.42 ± 0.96, odnosno 95.58 ± 0.74 % lijeka. Oslobađanje lijeka iz svih formulacija slijedilo je kinetiku po Higuchiju. Oslobađanje iz obloženih mikrosfera slijedilo je Korsmeyer-Peppasovu jednadžbu i kinetiku po Ficku. Studije stabilnosti pokazale su minimalnu razgradnju, te prihvatljivu stabilnost tijekom dvogodišnjeg skladištenja.

Novel drug delivery approaches on antiviral and antiretroviral agents

Viruses have the property to replicate very fast in host cell. It can attack any part of host cell. Therefore, the clinical efficacy of antiviral drugs and its bioavailability is more important concern taken into account to treat viral infections. The oral and parenteral routes of drug administration have several shortcomings, however, which could lead to the search for formulating better delivery systems. Now, a days novel drug delivery systems (NDDS) proved to be a better approach to enhance the effectiveness of the antivirals and improve the patient compliance and decrease the adverse effect. The NDDS have reduced the dosing frequency and shorten the duration of treatment, thus, which could lead the treatment more cost-effective. The development of NDDS for antiviral and antiretroviral therapy aims to deliver the drug devoid of toxicity, with high compatibility and biodegradability, targeting the drug to specific sites for viral infection and in some instances it also avoid the first pass metabolism effect. This article aims to discuss the usefulness of novel delivery approaches of antiviral agents such as niosomes, microspheres, microemulsions, nanoparticles that are used in the treatment of various Herpes viruses and in human immunodeficiency virus (HIV) infections.

Design and Evaluation of Voriconazole Loaded Solid Lipid Nanoparticles for Ophthalmic Application.

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 (308 ± 3.52 nm to 343 ± 3.51) compared to SLN prepared with ultrasonication method (234 ± 3.52 nm to 288 ± 4.58 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 −22.71 ± 0.63 mV to −28.86 ± 0.58 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.

Design and evaluation of HP-β-CD based voriconazole formulations for ocular drug delivery.

Systemic administration of voriconazole, a novel anti-fungal agent, is associated with adverse effects including visual disturbances and hepatic abnormalities. The purpose of this study was to improve the aqueous solubility of voriconazole using 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and to study the effect of addition of viscosity modifiers to these solutions. Statistical analysis was done by one-way analysis of variance followed by Dunnetts test. The phase solubility studies indicated that voriconazole solubility increased with increase in HP-β-CD concentration. Using a combination of chitosan 0.2%, BAK 0.01% and EDTA 0.01% in voriconazole- HP-β-CD based aqueous drops (1.5%, pH 7.0), a 3.9 times and 5.4 times higher Papp was obtained than with formulation without chitosan and control formulation (without chitosan and preservative), respectively. Thus, it could be concluded voriconazole aqueous drops formulated using HP-β-CD can be used topically for the treatment of fungal keratitis and the addition of chitosan to the voriconazole aqueous drops can produce significantly higher permeation.

Ocular insert for sustained delivery of gatifloxacin sesquihydrate: Preparation and evaluations

Background: Many polymeric systems have been used to fabricate ocular inserts for improve ocular bioavailability and retention to drug of which matrix systems have shown advantages of reduce dosing frequency and increased corneal residence time. The objective of the present investigation was to prepare and evaluate ocular inserts of gatifloxacin. Materials and Methods: Ocular insert was made from an aqueous dispersion of gatifloxacin, sodium alginate, polyvinyl alcohol, and glycerin by solvent casting method. Ocular insert (5.5 mm) was cross-linked by CaCl2 and was coated with Eudragit RL-100 or Eudragit RS-100. The ocular inserts were characterized for thickness; uniformity of weight, drug content uniformity, % moisture absorption or moisture loss, and surface pH. The in vitro diffusion studies were carried out by putting insert on Millipore membrane filter (0.8 μm) fixed between donor and receptor compartment of an all glass modified Franz diffusion cell. Results: The thickness and drug content of ocular insert were found in the range of 0.11 ± 0.003 to 0.24 ± 0.010 mm and 0.718 ± 0.002 to 0.867 ± 0.007 mg, respectively. The surface pH, % moisture absorption or moisture loss and weight variation values were obtained in satisfactory range. The cross-linked ocular insert coated with Eudragit RL-100 shows maximum drug permeation i.e. 89.53 % ± 0.43 at 11 h. The stability studies suggest that all ocular insert remained stable, showed lesser degradation rate and maximum shelf life. Conclusion: Ocular inserts of gatifloxacin were prepared successfully by using solvent casting method for sustained drug delivery. The cross-linked and Eudragit RL-100 coated ocular insert of gatifloxacin provides better in vitro drug release and sustained upto 11 h.

Design and evaluation of moxifloxacin hydrochloride ocular inserts

Design and evaluation of moxifloxacin hydrochloride ocular inserts The objective of the present investigation was to prepare and evaluate ocular inserts of moxifloxacin. An ocular insert was made from an aqueous dispersion of moxifloxacin, sodium alginate, polyvinyl alcohol, and dibutyl phthalate by the film casting method. The ocular insert (5.5 mm diameter) was cross-linked by CaCl2 and was coated with Eudragit S-100, RL-100, RS-100, E-100 or L-100. The in vitro drug drainage/permeation studies were carried out using an all-glass modified Franz diffusion cell. The drug concentration and mucoadhesion time of the ocular insert were found satisfactory. Cross-linking and coating with polymers extended the drainage from inserts. The cross-linked ocular insert coated with Eudragit RL-100 showed maximum drug permeation compared to other formulations. Dizajniranje i vrednovanje okularnih umetaka moksifloksacin hidroklorida Cilj rada bio je priprava i evaluacija okularnih umetaka moksifloksacina. Okularni umetak izrađen je od vodene suspenzije moksifloksacina, natrijevog alginata, polivinilnog alkohola i dibutil-ftalata metodom odlijevanja filma. Okularni umetak (promjera 5,5 mm) umrežen je pomoću CaCl2 i obložen Eudragitom S-100, RL-100, RS-100, E-100 ili Eudragit L-100. In vitro drenaža/permeacija lijeka proučavana je koristeći staklenu modificiranu Franzovu difuzijsku ćeliju. Koncentracija lijeka i vrijeme mukoadhezije okularnih umetaka bili su zadovoljavajući. Umrežavanje i oblaganje polimerima produljilo je drenažu iz umetaka. Umreženi okularni umetci obloženi s Eudragit RL-100 pokazali su veću permeaciju lijeka u odnosu na ostale pripravke.