Cross linked alginate gel beads as floating drug delivery system for cefdinir: optimization using Box–Behnken design

Radhakrishnan Praveen,Priya Ranjan Prasad Verma,Sandeep Kumar Singh,Jerome Karippamattom George 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.2

Regional absorption of several drugs necessitatesthe continuous monitoring of the movement of dosageform through gastro-intestinal tract. Sometimes it isimportant to deliver the drug at a particular physiologicalregion of the gastrointestinal tract for better effects. Floating delivery system is a prominent approach to releasethe drug in the gastric fluid. The objective of present studywas to formulate, evaluate and optimize cefdinir loadedintra-gastric floating beads of sodium alginate. Floatingalginate beads were prepared by ionic gelation methodaccording to Box–Behnken design with three factors variedat three levels. Uniform beads buoyant up to 24 h wereformed with rough surface and porous internal structure. Characterization by Fourier transform infrared spectroscopy,differential scanning calorimetry, thermo-gravimetricanalysis and powder x-ray diffractometry suggested anexcellent compatibility of drug with excipients and formulationprocess. The effect of selected independentvariables [amount of sodium alginate (X1), myristyl alcohol(X2) and cefdinir (X3) each at three levels] on thedependent variables [density (Y1), entrapment efficiency(Y2), time to release 20 % (Y3), cumulative percentage ofcefdinir released at 12th hour (Y4) and dissolution efficiency(Y5)] were studied using regression equations andresponse surface plots. The predicted and adjusted r² valueswere in reasonable agreement and the models weresignificant with p<0.05. Criteria were set for eachresponses and optimized formulation was preparedaccording to the software determined levels. The predictedand observed responses were in good agreement with lowpercent bias errors (<10 %), marking the validity of thedeveloped model. Thus, cefdinir loaded, extended release,intra-gastric floating gel beads of calcium alginate wereformulated and optimized.

Development, optimization and pharmacodynamic assessment of olanzapine based lipidic SNEDDS for proficient management of psychosis

Mohd Neyaz Ahsan,Priya Ranjan Prasad Verma 한국약제학회 2017 Journal of Pharmaceutical Investigation Vol.47 No.5

The purpose of this study was to demonstrate the use of 32 factorial design for the development and optimization of lipid based self nanoemulsifying drug delivery system of olanzapine using response surface methodology and to establish a functional relationship between two operating variables of Acconon E (X1) and Cremophor EL (X2). The response variables selected were optical clarity in Millipore water (Y1), Particle size in Millipore water (nm) (Y2), Particle size in 0.1 N HCl (nm) (Y3), Particle size in PB 7.4 pH (nm) (Y4), emulsification time (sec) (Y5) and time for 85 % of drug released (T85 %) (Y6). Compatibility studies using the fourier transform infrared spectroscopy, differential scanning calorimeter and X-ray diffraction studies indicated absence of any incompatibility between olanzapine and excipients used to prepare SNEDDS. Transmission electron microscopy of optimized formulations demonstrated the spherical globules morphology with no signs of coalescence and precipitation of drug. The in vitro hemolysis study and histological study showed the nondamaging effect of the OLZ-SNEDDS. Pharmacodynamic evaluation (Behavioural study) indicates better efficacy of olanzapine loaded SNEDDS.

Enhancement of in vitro dissolution and pharmacodynamic potential of olanzapine using solid SNEDDS

Mohd Neyaz Ahsan,Priya Ranjan Prasad Verma 한국약제학회 2018 Journal of Pharmaceutical Investigation Vol.48 No.3

The present research work focused on preparing a solidified lipidic self-nanoemulsifying drug delivery system (S-SNEDDS) by adsorbing liquid SNEDDS onto the surface of inert solid adsorbent (Aerosil-200) to improve the in vitro dissolution of poorly aqueous soluble drug, olanzapine and to evaluate their pharmacodynamic (Behavioral study) activity in Swiss albino mice. The liquid SNEDDS consisted of olanzapine, Acconon E and Cremophor EL. The powder flow properties were characterized using parameters viz. angle of repose (θ), Haussner’s ratio and Carr’s index. S-SNEDDS demonstrated good flow characteristics. The solid-state characterizations of S-SNEDDS by fourier transform infrared spectroscopy, differential scanning calorimeter and powder X-ray diffraction studies confirmed the amorphous behavior of olanzapine in the S-SNEDDS. Enhanced in vitro drug release and pharmacodynamic efficacy were attained from solidified- SNEDDS in comparison to olanzapine powder signifying the immense potential offered by S-SNEDDS and it could be a better alternative for oral administration of olanzapine.

Morphological and in vitro investigation of core–shell nanostructures of carvedilol using quality by design

Jerome K. George,Sandeep Kumar Singh,Priya Ranjan Prasad Verma 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.6

The present study aimed to develop an ideal nanostructured delivery (propylene glycol monocaprylatepolycaprolactone core–shell nanostructures) for a poorly soluble drug by quality-by-design (QbD) approach. Carvedilol (CVD) loaded polymeric nanocapsules were formulated by 3² factorial designs and established the functional relationships between the operating independent variables. An increase in polycaprolactone (PCL) content led to a rise in mean particle size, while the effect of Lutrol F127 was found statistically insignificant. Furthermore, it was observed that as the level of Lutrol F127 increases zeta potential decreases. However different levels of PCL did not significantly affected the zeta potential. The in vitro release of carvedilol from nanocapsule is contributed by the coupling of diffusion and erosion mechanism. Scanning electron microscopy, transmission electron microscopy (TEM) and atomic force microscopy (AFM) images showed the spherical nature of prepared optimized formulations OF1–OF3. TEM images illustrated spherical nanocapsules with a clearly distinctive oil core and PCL coating. The thickness of the core varied from 14.78 to 54.21 nm. The smooth surface of nanocapsules observed under AFM studies indicated no surface crystallization of CVD or other excipients used in preparing optimized formulations. The root mean square roughness and the average volume of optimized nanocapsules (OF1–OF3) ranged between 14.42–23.26 nm and 24.41–49.91 μm³, respectively. This study revealed the effectiveness of QbD for the preparation of optimized nanocapsules of CVD having desired attributes in the shortest possible time.

Pharmacokinetic evaluation of cefdinir-loaded floating alginate beads in rabbits using LC–MS/MS

Praveen R,Sandeep Kumar Singh,Priya Ranjan Prasad Verma 한국약제학회 2016 Journal of Pharmaceutical Investigation Vol.46 No.3

The present investigation aims to compare the pharmacokinetic parameters of Cefdinir in rabbits, from floating alginate (an anionic polysaccharide obtained from cell walls of brown algae) beads and conventional suspension, using a new LC–MS/MS method. Formulations equivalent to 20 mg/kg were administered orally to test and reference group and blood samples were collected at selected time intervals up to 24 h. Plasma concentrations of Cefdinir were determined using validated LC–MS/MS method and pharmacokinetic parameters were derived by non-compartment model. Statistically significant (p\0.05) increase in Cmax, Tmax, AUC0–? and MRT was observed in case of floating alginate beads, whereas KE and t1/2 remained relatively constant. MRT and tmax increased significantly as a result of controlled drug release. Relative bioavailability was 337.45 % for the floating beads. Thus, alginate based floating formulation improve the bioavailability (3.37 fold) of Cefdinir compared to suspension. The absorption of Cefdinir from floating beads was found mainly from duodenum (73.0 %) and Jejunum 1 and 2 (13.0 %).

Sustained delivery of cefdinir to upper gastrointestinal tract using calcium alginate beads: a formulation by design

Radhakrishnan Praveen,Sandeep Kumar Singh,Priya Ranjan Prasad Verma,Jerome Karippamattom George 한국약제학회 2014 Journal of Pharmaceutical Investigation Vol.44 No.6

The present research demonstrates the developmentand characterization of alginate based multiunitfloating dosage form for sustained delivery of cefdinir tothe upper gastrointestinal tract. The method involved ionicgelation of sodium alginate solution containing suspendeddrug and myristyl alcohol (release modifier and buoyancyregulator) by calcium ions followed by freeze drying. Fourier transform infrared spectroscopy and differentialscanning calorimetry studies revealed that there were noincompatibilities between drug and excipients. The effectof various process variables; amount of sodium alginate,myristyl alcohol and cefdinir; on critical parameters likedrug loading, particle size and mean dissolution time(MDT) was modelled using Box–Behnken design andstudied using response surface plots and regression equations. The observed and predicted r2 values were inagreement in case of all the responses which marks thevalidity of developed model. The particle size, drug loadingand MDT were found to be strongly dependent on thevariables studied. The beads showed high drug loading upto 65.41 % and extended drug release up to 24 h in 0.1 Nhydrochloric acid. The beads exhibited 100 % buoyancywithout any lag time up to 24 h despite of the high drugloading. The mechanism of drug release was found to beFickian diffusion.

Preformulation and physicochemical interaction study of furosemide with different solid lipids

Hasan Ali,Sandeep Kumar Singh,Priya Ranjan Prasad Verma 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.4

The aim of the present work was to prepare and characterize the matrices of Furosemide (FRSM) with different solid lipids (Compritol 888 ATO, Hydrokote C, Imwitor 491, Imwitor 372P, and Witepsol H12) using Fourier transform infrared (FTIR), Raman, differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy. The solubility of FRSM in various solid lipids followed the order of; Compritol 888 ATO>Witepsol H12>Hydrokote C>Imwitor 491>Imwitor 372. FTIR, Raman, DSC and XRD studies indicated no chemical interactions with Compritol 888 ATO, Imwitor 491 and Imwitor 372P. Scanning electron microscopic images of lipids, melted lipids, FRSM and FRSM-lipid matrices showed different morphological characteristics. In vitro drug release study showed the sustained release of drug from all lipid-matrices that followed Higuchi and Korsmeyer–Peppas model except FRSM-Hydrokote matrix. The best fit model of FRSMHydrokote matrix was zero order (R² = 0.978). Conclusively, Compritol 888 ATO was selected as lipid of choice owing to maximum solubility, least chemical interaction and better sustained release profile.