Design of quetiapine fumarate loaded polyethylene glycol decorated graphene oxide nanosheets: Invitro-exvivo characterization.

Quetiapine Fumarate (QF) is an atypical antipsychotic with poor oral bioavailability (9%) due to its low permeability and pH-dependent solubility. Therefore, this study aims to design QF-loaded polyethylene glycol (PEG) functionalized graphene oxide nanosheets (GON) for nasal delivery of QF. In brief, GO was synthesized using a modified Hummers process, followed by ultra-sonication to produce GON. Subsequently, PEG-functionalized GON was prepared using carbodiimide chemistry (PEG-GON). QF was then decorated onto the cage of PEG-GON using the π-π stacking phenomenon (QF@PEG-GON). The QF@PEG-GON nanocomposite underwent several spectral characterizations, in vitro drug release, mucoadhesion study, ex vivo diffusion study, etc. The surface morphology of QF@PEG-GON nanocomposite validates the cracked nature of the nanocomposite, whereas the diffractograms and thermogram of nanocomposite confirm the conversion of QF into an amorphous form with uniform distribution in PEG-GON. Moreover, an ex vivo study of PEG-GON demonstrates superior mucoadhesion capacity due to its surface functional groups and hydrophilicity. The percent drug loading content and percent entrapment efficiency of the nanocomposite were found to be 9.2±0.62% and 92.3±1.02%, respectively. The developed nanocomposite exhibited 43.82±1.65% drug release within 24h, with the Korsemeyer-Peppas model providing the best-fit release kinetics (R2: 0.8614). Here, the interlayer spacing of PEG-GON prevented prompt diffusion of the buffer, leading to a delayed release pattern. In conclusion, the anticipated QF@PEG-GON nanocomposite shows promise as a nanocarrier platform for nasal delivery of QF.

Bio-fabrication and statistical optimization of polysorbate 80 coated chitosan nanoparticles of tapentadol hydrochloride for central antinociceptive effect: in vitro-in vivo studies.

Tapentadol hydrochloride (TPD) is a novel analgesic with two mechanisms of actions: agonist activity at the µ-opioid receptor and norepinephrine reuptake inhibition. The conventional delivery of TPD is problematic, owing to its extensive first pass metabolism, low lipophilicity and short half-life that leads to low bioavailability (32%). The intent of the present work was aimed at bio-fabrication of polysorbate 80 coated chitosan nanoparticles (CS-NPs) for CNS targeting of TPD using factorial design approach for enhanced delivery of drug. TPD-CS-NPs were prepared by ionic gelation technique and optimized using 23 factorial design of experiment. The effect of polymer (CS) and cross linker (TPP) concentration was studied on particle size (PS) and entrapment efficiency (EE %). Formulation CNP6 was considered desirable with optimal EE % (87.1 ± 0.4%), PS (329.3 ± 1.0 nm), zeta potential (30.4 ± 0.7 mV) and cumulative drug release of 73.5 ± 2.9% in 24 h. Differential scanning calorimetry revealed the absence of any chemical interaction between TPD, CS, and TPP while SEM study confirmed spherical morphology. In vivo pharmacodynamic studies on rat model verified that pure drug was unable to show considerable antinociceptive activity owing to its hydrophilic nature, conversely polysorbate 80 coated TPD-CS-NPs showed a significant antinociceptive effect over a period of 24 h, which is evidence for brain targeting of TPD-CS-NPs. Accelerated stability studies of optimized batch demonstrated a negligible change in the average PS and EE % after storage at 25 ± 2 °C/60 ± 5% RH (relative humidity) for the period of three months. The ANOVA results for the dependent variables demonstrated that the model was significant (P values < 0.05) for response variables. Above finding suggested practicability of investigated system for effective targeting of many therapeutic agents in the treatment of many life threatening CNS disorders.

Nanostructured lipid carriers as a potential vehicle for Carvedilol delivery: Application of factorial design approach.

Present invention relates to design of nanostructured lipid carriers (NLC) to augment oral bioavailability of Carvedilol (CAR). In this attempt, formulations of CAR-NLCs were prepared with glyceryl-monostearate (GMS) as a lipid, poloxamer 188 as a surfactant and tween 80 as a co-surfactant using high pressure homogenizer by 2(3) factorial design approach. Formed CAR-NLCs were assessed for various performance parameters. Accelerated stability studies demonstrated negligible change in particle size and entrapment efficiency, after storage at specified time up to 3 months. The promising findings in this investigation suggest the practicability of these systems for enhancement of bioavailability of drugs like CAR.

Sonication-assisted drug encapsulation in layer-by-layer self-assembled gelatin-poly (styrenesulfonate) polyelectrolyte nanocapsules: process optimization.

We report the development of Layer-by-Layer (LbL) polyelectrolyte self-assembled nanocrystalline drug-delivery platform using two experimental factors, namely the number of coatings and temperature during deposition with three varying levels. The optimized formulation (Fopt) was assessed for zeta potential and particle size using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM). Charge reversal along with an increase in particle size confirmed coating of polyelectrolyte on drug nanocrystals. The FT-IR study revealed no signs of incompatibility or change in formulation property during preformulation and stability study. This fact was further supported by DSC results.

Fabrication and statistical optimization of surface engineered PLGA nanoparticles for naso-brain delivery of ropinirole hydrochloride: in-vitro-ex-vivo studies.

Ropinirole hydrochloride (RPN), a nonergot dopamine D2-agonist used in the management of Parkinson's disease, has poor oral bioavailability (52%) due to extensive hepatic metabolism. The intent of present research work was aimed at design and statistical optimization of RPN-loaded poly (lactic-co-glycolic acid) (PLGA)-based biodegradable nanoparticles (NPs) surface modified using natural emulsifier, vitamin E (d-α-tocopheryl polyethylene glycol 1000 succinate [TPGS]) for direct nose-to-brain delivery in order to avoid hepatic first-pass metabolism, and improve therapeutic efficacy with sustained drug release. RPN-NPs were prepared by modified nanoprecipitation technique and optimized using 2(3) factorial design of experiment. The effect of polymer and emulsifier concentration was evaluated on particle size and entrapment efficiency (EE%). Formulation PL6 was considered as desirable with highest EE% (72.3 ± 6.1%), PS (279.4 ± 1.8 nm), zeta potential (-29.4 ± 2.6 mV), and cumulative drug diffusion of 96.43 ± 3.1% in 24 h. The ANOVA results for the dependent variables demonstrated that the model was significant (p value < 0.05) for response variables. Histopathological study of optimized batch (PL6) demonstrated good retention of NPs with no severe signs of damage on the integrity of nasal mucosa. Differential scanning calorimetry revealed the absence of any chemical interaction between RPN, PLGA, and TPGS while SEM study confirmed spherical shape of optimized NPs. Accelerated stability studies of freeze-dried optimized batch demonstrated negligible change in the average PS and EE% after storage at 25 ± 2 °C/60 ± 5% (relative humidity (RH) for the period of three months. The promising results of optimized batch suggested practicability of investigated system for enhancement of bioavailability and brain targeting of CNS acting drugs like RPN.

Design and development of novel dual-compartment capsule for improved gastroretention.

The aim of the proposed research work was to develop a novel dual-compartment capsule (NDCC) with polymeric disc for gastroretentive dosage form, which will ultimately result in better solubility and bioavailability of Ofloxacin. Floating ring caps were formulated by using different natural polymers, separating ring band and swellable polymer located at the bottom of capsule. Formulated ring caps were assessed for coating thickness, In vitro buoyancy, In vitro drug release, release kinetics and stability studies. Coating attained by the capsule shell was found to be 0.0643 mm. Depending on nature of natural polymer used, most of the formulations showed buoyancy for more than 9 hrs. Developed formulation demonstrated considerably higher drug release up to 9 hrs. The developed formulation F(E2) depicted the drug release according to Korsmeyer-Peppas model. There was not any significant change in performance characteristics of developed ring caps after subjecting them to stability studies. The present study suggests that the use of NDCC for oral delivery of Ofloxacin could be an alternative to improve its systemic availability which could be regulated by the floating approach. The designed dosage system can have futuristic applications over payloads which require stomach-specific delivery.

Stimuli-sensitive layer-by-layer (LbL) self-assembly systems: targeting and biosensory applications.

Stimuli-sensitive layer-by-layer (LbL) self-assembly systems have generated much interest among researchers worldwide due to the simplicity of the process by which they are produced and their numerous applications in drug delivery. LbL self-assembly systems involve simple alternative adsorption of oppositely charged polyelectrolytes on core materials and are thus considered to be promising tools for drug delivery and biosensing. Here, we discuss the latest findings from research into LbL systems, with special emphasis on drug delivery systems. This review highlights various stimuli-responsive LbL systems and their targeting and biosensory applications. For the convenience of readers, these stimuli-responsive LbL systems are classified as exogenous stimuli-responsive LbL systems and endogenous stimuli-responsive LbL systems.

Design and statistical optimization of osmotically driven capsule based on push-pull technology.

In present investigation attempt was made to develop and statistically optimize osmotically active capsule tailor made from the concept of bilayer (push-pull) osmotic tablet technology. The capsule was comprised of active (drug) and push (osmogen) layer. Active layer was compressed in form of tablet by mixing known amount of drug and formulation excipients. Similarly push layer was made by compressing Mannitol with formulation excipients. Finally, both layers were packed in hard gelatin capsule having small aperture at top and coated with semipermeable membrane to form osmotically active capsule. Formulated and optimized capsules were characterized for Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetric (DSC), scanning electron microscopy, In-vitro drug release study and Release models and kinetics. Statistically optimized formulation showed good correlation between predicted and experimented results, which further confirms the practicability and validity of the model.