Release Of Olanzapine Research Articles

Design and Optimization of Elanzapine Drug Release with Polyoxazoline Based Hydrogel

Due to the fact that Elanzapine is prescribed orally and by injection for psychotic and schizophrenic disorders, and depending on the type of disease, these people are prevented from swallowing the drug; therefore, checking the injectable form of the drug with controlled release, which increases the release of the drug to one week with a single injection, is important. On the other hand, one of the most important biodegradable polymers that have the adhesive property of Elanzapine is Polyoxazoline, so the aim of this study is to design a slow release system, considering the short half-life of this drug and the need for a large number of doses and the patient's lack of cooperation for treatment. The drug is based on Polyoxazoline, which can reduce the consumption and, consequently, the toxicity and accumulation of the drug in the body. Mathematical heart direction, the forecast of different conditions will be presented, and also obtaining the optimal conditions and the final formulation is one of the main goals of this study. In this research, the release of olanzapine on the matrix loaded with olanzapine, the morphological characteristics of the matrix, the thermal characteristics of the matrix and the rheological characteristics of the matrix have been investigated. The release of olanzapine in the examined gels lasted for more than 168 hours, which was a sign of the slow release system, which is the main goal of this project. Several models were used to investigate the release kinetics of olanzapine, and among them, the Higuchi equation showed the best degree of regression with experimental data. By increasing the percentage of Elanzapine, the process of changes in viscosity goes out of the linear state; on the other hand, the difference between the optimum matrix viscosity of 3 and 4% of Elanzapine is small.

Mass Transfer of Olanzapine in the Liquid Lamellar Phases Formed by the Self-assembly of Glycerol Monooleate (GMO): Experimental Data and Mathematical Modeling

Aims: The present study aimed to optimise the formulation of Olanzapine (OZ)-loaded liquid lamellar phase by using Response Surface Methodology (RSM). Background: In this study, poly (2-ethyl-2-oxazoline) (PEOZ) was selected to modify liquid lamellar phases. The OZ was released from the phases mainly through swelling and diffusion-controlled mechanism simultaneously. Objective: Additionally, two types of mathematical models, based on the lumped and diffusion approaches, were presented for the diffusional release of OZ from the liquid lamellar phases, the second of which was solved with an analytical solution. The controlled release profiles of the models were compared with the in vitro experimental release profiles. Method: Further, the Box-Behnken experimental design was employed to design the liquid lamellar phase with the three factors, including the weight ratio of water/GMO (w/w) (X1) and PEOZ/GMO (w/w) (X2), and the percentage of OZ (X3). The liquid lamellar phases were prepared based on the top-down method, followed by fragmentation by sonication. Furthermore, the diffusion coefficients of the liquid lamellar phases were calculated, and the effects of variables were evaluated on particle size and diffusion coefficient, as well as the constant of the lumped model. Result: The results revealed an increase in particle size following an enhancement in water level in the liquid lamellar phases, as well as less aggregation with the addition of PEOZ. Conclusion: The generated model was validated by comparing the experimental data and predicted model values graphically, the results of which represented compatibility between the lumped model and experimental data.

D-α-Tocopherol polyethylene glycol succinate and stearoylmacrogol glycerides biomaterial based nanostructured mixed micelles as nose-to-brain targeting drug delivery system

ABSTRACT Olanzapine (OLA), a first atypical antipsychotic moleculethat experiences low brain permeability because of efflux by P-glycoproteins (Pgp) in the brain and extensive hepatic first-pass metabolism. The present investigation intended to design OLA-loaded mixed micelles (MM) and study their nose-to-brain targeting capability. OLA-MM was prepared by a mixture of d-α-tocopheryl polyethylene glycol 1000 succinate and gelucire®44/14 (stearoylmacrogol glycerides) (OLA-TPGL-MM) using the solvent evaporation technique. OLA-TPGL-MM was studied for various physiochemical properties, in-vitro release, ex-vivodrug permeation and in-vivo pharmacokinetic potential in male Wister rats as compared to OLA alone. Developed OLA-TPGL-MM showed particle size, negative zeta potential and entrapment efficiency of 125 nm, −5.97 mV and > 83%, respectively. OLA-TPGL-MM showed 2.12 and 1.85-fold improvement in in-vitro and ex-vivo OLA release and permeation. Substantially higher values for intranasal (i.n) OLA-TPGL-MM in drug targeting efficiency (265.36%), drug targeting index (1.82) and direct transport percentage (64.36%) indicating the potential of non-invasive OLA-loaded MM nose-to-brain targeting delivery system. TheTPGS and gelucire®44/14 based MM has a great potential for the safe and effective delivery of antipsychotic molecules in the treatment of CNS disorders.

DEVELOPMENT AND EVALUATION OF A POLOXAMER- AND CHITOSAN-BASED IN SITU GEL-FORMING INJECTABLE DEPOT

Objective: The present study is intended to investigate the applicability of poloxamer- and chitosan-based temperature induced in situ injectable gelling depot for once a week therapy as an intramuscular injection employing olanzapine as a model drug.
 Methods: The thermosetting gel was prepared by admixture of a solution of poloxamer P127 and a solution of olanzapine and chitosan in aqueous acetic acid. The resultant formulation was characterized for gelation temperature, gelation time, viscosity, syringeability, pH, drug content, and in vitro drug release. The in vitro release of olanzapine from the gelled depot was followed using USP paddle type II apparatus in conjunction with a dialysis bag. The gel was injected ex vivo into chicken muscle and observed by subsequent dissection.
 Results: The formulation was designed to have a phase transition temperature of 34°C and gelled in <10 s at 37°C. Addition of chitosan imparted favorable rheological properties to the poloxamer gel and resulted in a pseudoplastic mixture with low viscosity in the sol state and higher viscosity post gelation. The preparation had a pH of 5.4, appropriate drug content and readily passed through a 20 gauge needle. The release of olanzapine was unhindered by the dialysis bag. Following an initial bust, a sustained, zero-order release of the remainder of drug was observed up to 9 days. The injectable was found to form a compact depot when evaluated ex vivo.
 Conclusion: The developed system showed several features which make it a suitable vehicle for sustained intramuscular delivery of drugs.

Mechanistic insights of the enhancement effect of sorbitan monooleate on olanzapine transdermal patch both in release and percutaneous absorption processes

In this paper, based on the optimized formulation of olanzapine (OLN) transdermal patch, the role of sorbitan monooleate (SP) in OLN release and percutaneous absorption processes was probed in vitro and in vivo. Rheological test, DSC, FT-IR and molecular modeling were conducted to elucidate the effect of SP on the release process of OLN from transdermal patch. Additionally, the action of SP on the percutaneous absorption process was probed using tape stripping transdermal experiment, confocal laser scanning microscopy (CLSM), ATR-FTIR and molecular docking. The results showed that the hydrogen bonding interaction between OLN and pressure sensitive adhesive (PSA) was weakened by SP, which resulted in a decrease in the cohesive interaction between polymer chains and an increase in the formation of free volume of PSA, thus, the release of OLN from patch was promoted. Meanwhile, the OH groups of SP interacted with the polar head groups of the ceramides, which increased the fluidity of the skin lipids, thereby improved the ability of OLN percutaneous absorption. In summary, this study demonstrated that not only the release but also the percutaneous absorption processes were promoted by SP. This study provided comprehensive molecular level understanding on the effect of penetration enhancer on transdermal patch and strategies for rationally selection of chemical enhancer for transdermal drug delivery systems.

Mesoporous Hydroxyapatite as Olanzapine Carrier Provides a Long-Acting Effect in Antidepression Treatment.

An antidepressant carrier was designed to maintain over 2 weeks of constant medication release. The carrier was injected into muscle, where cellular activity was employed to achieve the goal of constant release. Mesoporous hydroxyapatite (mesoHAP) was synthesized into an adequate size by a coprecipitation method; it then went through a series of hydrophobic surface modifications for olanzapine (OLZ) loading by physical absorption to produce mesoHAP-OLZ. Because of its hydrophobic nature, OLZ was not effectively released from mesoHAP-OLZ in an aqueous environment. However, once engulfed by macrophages, the lysosome/endosome hybrid ruptured due to alterations in osmotic pressure, resulting in the release of OLZ into the cytoplasm. OLZ was then exocytosed to the extracellular space due to a high calcium ion (Ca(2+)) concentration and finally reached the blood circulation. Our findings provide a useful treatment strategy to achieve long-term drug release with a single intramuscular (IM) injection, helping to solve the problem of nonadherent medication intake that often occurs in antidepressant therapy.

Investigations of the effect of the lipid matrix on drug entrapment, in vitro release, and physical stability of olanzapine-loaded solid lipid nanoparticles

The purpose of this research was to study the effect of the lipid matrix on the entrapment of olanzapine (OL). OL-loaded solid lipid nanoparticles (SLNs) were prepared using lipids like glyceryl monostearate (GMS), Precirol ATO 5 (PRE), glyceryl tristearate (GTS), and Witepsol E85 (WE 85)--and poloxamer 407 and hydrogenated soya phosphatidylcholine as stabilizers--using a hot melt emulsification high-pressure homogenization technique, and then characterized by particle size analysis, zeta potential, differential scanning calorimetry (DSC), and powder X-ray diffraction (pXRD). Homogenization at 10,000 psi for 3 cycles resulted in the formation of SLNs with a mean particle size of approximately 190 nm for the 4 lipids investigated. The highest partition coefficient for OL between the melted lipid and pH 7.4 phosphate buffer (pH 7.4 PB) was obtained with GTS. The entrapment efficiency was in the following order: GTS SLNs > PRE SLNs > WE 85 SLNs > GMS SLNs. DSC and pXRD showed that much of the incorporated fraction of OL existed in the amorphous state after incorporation into SLNs. A sharp increase in the flocculation of the SLN dispersions was observed upon addition of 0.6 M aqueous sodium sulfate solution. Nanoparticle surface hydrophobicity was in the following order: GTS SLNs > PRE SLNs > WE 85 SLNs > GMS SLNs. A significant increase in size and zeta potential was observed for GTS SLN and WE 85 SLN dispersions stored at 40 degrees C. Release of OL from the SLNs was sustained up to 48 hours in pH 7.4 PB and obeyed Higuchi's release kinetics.