Sunil Kamboj

Physicochemical and functional performance of pectin extracted by QbD approach from Tamarindus indica L. pulp.

The aim of present investigation was to utilize quality by design (QbD) approach for extraction of tamarind pectin (TP) from Tamarindus indica L. pulp employing purity descriptors as indicator. The software generated quadratic equations showed significant effect of polarity index as compared to pulp concentration and boiling temperature on percentage yield and purity characteristics of TP. An insignificant effect on purity descriptors and percentage yield of TP upon replacement of acetone with methanol during predicted vs observed correlation studies (being similar polarity index of 5.1) pointed towards overwhelming influence of solvent polarity. Further, the FTIR-ATR, (1)H NMR, DSC and mass spectroscopy suggested TP was rhamnogalacturonan pectin with no tartaric acid content. TP was found to have significantly higher antioxidant activity as compare to apple pomace pectin, citrus peel pectin and commercial pectin. Overall, the physicochemical properties and antioxidant potential of TP could be utilized as an excipient for food and pharmaceutical industry.

Development of aprepitant loaded orally disintegrating films for enhanced pharmacokinetic performance

The present investigation was aimed to prepare orally disintegrating films (ODFs) containing aprepitant (APT), an antiemetic drug employing pullulan as film forming agent, tamarind pectin as wetting agent and liquid glucose as plasticizer and solubiliser. The ODFs were prepared using solvent casting method. The method was optimized employing 3(2) full factorial design considering proportion of pullulan: tamarind pectin and concentration of liquid glucose as independent variables and disintegration time, wetting time, folding endurance, tensile strength and extensibility as dependent variables. The optimized ODF was evaluated for various physicochemical, mechanical, drug release kinetics and bioavailability studies. The results suggested prepared film has uniform film surface, non-sticky and disintegrated within 18s. The in-vitro release kinetics revealed more than 87% aprepitant was released from optimized ODF as compared to 85%, 49%, and 12% aprepitant release from marketed formulation Aprecap, micronized aprepitant and non micronized aprepitant, respectively. The results of animal preference study indicated that developed aprepitant loaded ODFs are accepted by rabbits as food material. Animal pharmacokinetic (PK) study showed 1.80, 1.56 and 1.36 fold enhancement in relative bioavailability for aprepitant loaded ODF, Aprecap and micronized aprepitant respectively, in comparison with non-micronized aprepitant. Overall, the solubilised aprepitant when incorporated in the form of aprepitant loaded ODF showed enhanced bioavailability as compared to micronized/non-micronized aprepitant based oral formulations. These findings suggested that aprepitant loaded ODF could be effective for antiemesis during cancer chemotherapy.

Quality-by-design based development of a self-microemulsifying drug delivery system to reduce the effect of food on Nelfinavir mesylate.

Poor aqueous solubility and moderate permeability of Nelfinavir mesylate (NFM) leads to high variability in absorption after oral administration. To improve the solubility and bioavailability of NFM, the self microemulsifying drug delivery system (SMEDDS) was developed. For this purpose, Quality by design (QbD) approach employing D-optimal mixture design was used to prepare SMEDDS of NFM. Further, the software generated numerically optimized SMEDDS were developed by utilizing desirability function. Maisine 35-1, Tween 80, and Transcutol HP were identified as oil, surfactant, and co-surfactant that had best solubility for NFM. Ternary phase diagrams were plotted to identify the self-emulsification region. Dissolution of putative NFM in simulated fasted or fed small intestinal conditions, respectively, predicted that there is a positive food effect. However, NFM loaded SMEDDS showed absence of food effect with no significant difference in dissolution performance either in Fasted or fed state simulated intestinal fluid (FaSSIF or FeSSIF) biorelevent dissolution media. The prepared SMEDDS were thermodynamically stable with droplet size (121 nm), poly dispersity index (PDI) (0.198) and emulsification time (<1 min). Transmission electron microscopy (TEM) analysis confirmed the spherical shape of the reconstituted SMEDDS droplets. The ex vivo performance revealed 4.57 fold enhancement in the apparent permeability of NFM as compared to NFM suspension. The animal pharmacokinetic analysis in New Zealand strain rabbits indicated food effect on pure NFM suspension. However, absence of food effect and 3.5-3.6 fold enhancement in the oral bioavailability was observed when NFM was formulated into SMEDDS. Thus, it could be envisaged that development of SMEDDS formulation of NFM could be one of the best alternative to enhance oral bioavailability of NFM.

Aprepitant loaded solid preconcentrated microemulsion for enhanced bioavailability: A comparison with micronized Aprepitant.

Aprepitant (APT) is a lipophilic, poorly water soluble drug with moderate permeability characteristic. Therefore, we aimed to improve solubility as well as permeability that could possibly improve oral bioavailability of APT. For this purpose, Quality by design (QbD) approach employing simplex lattice mixture design was used to prepare solid preconcentrated microemulsion (S-PCM). Further, the software generated numerically optimized S-PCM formulations were developed by utilizing desirability function. The spectral attributes (powder X-ray diffraction, ATR-FTIR, and differential scanning calorimetry) of S-PCM formulations suggested that APT was present in amorphous form. The results of droplet size (150-180 nm), zeta potential (-13 to -15 mV), poly dispersity index (PDI) (0.211-0.238) and emulsification time (<1 min), of these S-PCM formulations (SP1, SP2 and SP3) suggested spherical shape morphology (Transmission electron microscopy) with thermodynamic stability. The comparison of in vitro/ex vivo behavior of S-PCM (SP1) with micronized and non-micronized formulations of APT suggested 2-fold and 5-fold enhancement in solubility and permeability, respectively. This was further evident from pharmacokinetic studies in rabbits that showed 1.5-fold enhancement in bioavailability of S-PCM with respect to micronized APT. Thus, it could be envisaged that development of S-PCM formulation of APT is the best alternative to micronization technology based APT formulations reported earlier.

QbD based synthesis and characterization of polyacrylamide grafted corn fibre gum

The aim of present investigation was to utilize quality by design approach for the synthesis of polyacrylamide corn fibre gum (PAAm-g-CFG) from corn fibre gum (CFG) by varying concentration of acrylamide and initiator. The spectral analysis (ATR-FTIR, 1H NMR, DSC, X-ray and Mass spectroscopy) was conducted to assure grafting copolymerization of CFG with acrylamide. The powder flow properties confirm the porous nature of PAAm-g-CFG. The grafted copolymer dispersion showed shear thinning behaviour that follows Herschel Bulkley model. The viscoelastic analysis suggested viscous liquid like nature of PAAm-g-CFG and its viscosity increases with increase in concentration of PAAm-g-CFG. The mucoadhesive strength of synthesized PAAm-g-CFG was found to be higher than moringa oleifera gum, karaya gum, guar gum, xanthan gum, chitosan and gelatin. Further, the results pointed toward enhanced thermal stability of PAAm-g-CFG. Thus, PAAm-g-CFG has a great potential to be used in food and pharmaceutical industry.

Investigating the potential of Tamarindus indica pectin–chitosan conjugate for reducing recovery period in TNBS induced colitis

The present study was aimed at exploiting the wound healing applications and tablet coating potential of Tamarindus indica pectin-chitosan (PCH) conjugate for reducing recovery period from TNBS induced colitis. The PCH (60:40, 3% w/v) solution when spray coated followed by drying at 50°C created hydrophobic surface, that may be due to interaction of pectin with chitosan as evident from temperature ramping rheological investigations. Further, the 15% w/v coating was sufficient to prevent Mesalamine (Ma) release in pH 1.2. The AUC and AUMC of PCH coated tablets were 1.98 and 17.69 fold increased as compared to uncoated tablets. A synergistic therapeutic effect of PCH conjugate with Ma was evident from the colon/body weight ratio, clinical activity and damage score. Overall, the findings suggested PCH and Ma (20mg) reduces the recovery period from 5 to 4days with reduction in dose.

Formulation optimization of aprepitant microemulsion-loaded silicated corn fiber gum particles for enhanced bioavailability.

Abstract The present investigation was aimed at development of silicate corn fiber gum (SCFG) particles as superior solid carrier for the preparation of Aprepitant (APT)-loaded self-emulsifying powder (SEP) system. 24 D-optimal mixture design with three level process variables was employed to develop SCFG particles, utilizing flow descriptors and hydrophobicity descriptors as response variables. The results indicated that blending of CFG (51.4% w/w) and magnesium silicate (MS) (48.6% w/w) using freeze-drying technique was found to have highest desirability (0.904). The developed SEP showed highest oil desorbing capacity, low self-emulsification time and highest drug content. It was observed that SCFG-SEP (F2 formulation) showed lowest PDI (0.2445 ± 0.03) as well as smallest particle size (127 ± 5.8 nm). The droplets were uniform and maintain their integrity after reconstitution (TEM analysis). Furthermore, APT-loaded SEP showed enhanced in vitro dissolution (4 folds) and ex vivo performance (7-fold enhanced Papp) as compared to pure APT. Furthermore, in vivo pharmacokinetic study showed that significant enhancement (p > 0.05) in Cmax was evident with APT-loaded F2 (SCFG-SEP) (1.93-fold) and F4 (Aerosil 200-SEP) (1.58-fold). The data also suggested increase in absorption rate when APT incorporated into SCFG-SEP. Thus, findings pointed toward enhanced bioavailability of APT when loaded into SCFG particles. Overall, the developed SCFG particles could be considered as a better alternative to already available solid carrier(s).

A QbD approach for the fabrication of immediate and prolong buoyant cinnarizine tablet using polyacrylamide-g-corn fibre gum

The main hurdle in the oral delivery of cinnarizine is its supersaturation, precipitation and re-dissolution process, influencing the oral bioavailability. To overcome this problem, an attempt was made to develop immediate and prolong buoyant tablet of cinnarizine. For this purpose, polyacrylamide-g-corn fibre gum (p-CFG) was synthesized as mucoadhesive cum swellable polymer and it was compared with already used HPMC K4M polymer. The central composite design with two numeric and one categorical factor was choosen to optimize conc. of p-CFG (X1), concentration of NaHCO3 (X2) and type of effervescent agents (X3). The bioadhesive strength of p-CFG tablet was 2.4 times higher than HPMC K4M containing tablet. The formulation composition comprises of p-CFG (64.3%), sodium bi‑carbonate (12.9%) and citric acid (2%) (FCNZ) fulfilled the maximum requirement of an optimized formulation. The in-vivo animal pharmacokinetic performance revealed larger plasma half-life and reduced elimination rate as compared to CNZ suspension. Interestingly, the absorption of CNZ from optimized formulation was 3 times enhanced than from CNZ suspension. Overall, the enhancement in the oral bioavailability of CNZ was evident that is due to its prolonged gastric residence time. Furthermore, the swelling associated floating followed by mucoadhesive nature of tablet was observed by X-ray imaging studies.

Lipid based delivery of Efavirenz: An answer to its erratic absorption and food effect

ABSTRACT The current investigation entails systematic development of EFV (Efavirenz) loaded isotropic mixture prepared with long chain triglycerides for obliterating food associated variability and minimizing the erratic absorption behavior. For this purpose, the optimized isotropic mixture (EF1) consists of Maisine 35‐1 (20%), Transcutol HP (17.7% w/w) and Cremophor RH 40:Labrasol (1:1) (62.3% w/w) was formulated by employing D‐optimal mixture design that after numerical optimization showed highest desirability of 0.995. Further, the dissolution behavior of EFV suspension in biorelevant dissolution medias simulate the fed and fasted small intestine conditions, clearly anticipated that there is an influence of food effect for EFV. However, when EFV loaded into isotropic mixture, the food effect was abolished and no significant difference was seen in biorelevant dissolution medias. The tissue distribution of EFV from EF1 follows order: blood plasma > heart > brain > lymph nodes > liver. Interestingly, the in‐vivo animal pharmacokinetic performance showed positive food effect after administration of EFV suspension and marketed formulation. However, the developed formulation (EF1) nullifies this food effect. In nutshell, these studies suggested significant enhancement in the biopharmaceutical attributes of a stable and robust EFV loaded isotropic mixture. Graphical abstract Figure. No Caption available.

Quality by Design Based Fabrication of Iron Oxide Induced Mucoadhesive Microspheres for Enhanced Bioavalibility of Cinnarizine

BACKGROUND The study was aimed to enhance the mucoadhesive potential of Eudragit RS 100 and RL 100 using iron oxide. METHODS Microspheres of Eudragit RS/RL100, containing cinnarizine, were prepared by emulsification solvent evaporation technique employing 32 full factorial design. Eudragit RS or RL (X1) and iron oxide (X2) concentrations were the independent variables. Particle size, entrapment efficiency, mucoadhesion, zeta potential and t90% were the response variables. Microspheres when characterized by FTIR-ATR and DSC confirm entrapment of drug. RESULTS SEM analysis of microspheres exhibits roughness/micropores responsible for drug release. Particle size of Eudragit RS and Eudragit RL microspheres was found to increase from 275.60±2.68 to 438.72±22.73 nm and 283.14±1.95 to 475.55±29.66 nm. Incorporation of iron oxide increases zeta potential from 0.88±0.18 to 10.74±1.78 mV and 1.12±0.11 to 14.44±2.44 mV for Eudragit RS and RL microspheres, respectively. Highest mucoadhesion and zeta potential were obtained when 4.5% w/v of X1 and 20% w/v of X2 were used in the formulation of microspheres. CONCLUSION The r2 values were significantly higher (P < 0.01) for the Langmuir equation as compared to Freundlich equation, indicating the involvement of electrostatic forces in the specific adsorption of mucin on to Eudragit microspheres. In vivo study indicates 2.5 to 3 times increased bioavailabity of cinnarizine through mucoadhesive microspheres.