Design, Synthesis and Studies on Novel Polymeric Prodrugs of Erlotinib for Colon Drug Delivery

Aims: In the present study, polymer-drug conjugates were synthesized based on azo-bond cleavage drug delivery approach for targeting erlotinib as anticancer drug specifically to the colon for the proficient treatment of colon cancer. Background: Colon cancer (CC) is the third commonly detected tumor worldwide and it make up about 10 % of all cases of cancers. Most of the chemotherapeutic drugs available for treating colon cancer are not only toxic to cancerous cells but also to the normal healthy cells. Among the various approaches to get rid of the adverse effects of anticancer agents, prodrugs are one of the most imperative approaches. Objective: The objective of the study is to chemically modify the erlotinib drug through azo-bond linkage and suitable spacer which will be finally linked to polymeric backbone to give desired polymer linked prodrug. The azo reductase enzyme present in colon is supposed to cleave the azo-bond specifically and augment the drug release at the colon. Methods: The synthesized conjugates were characterized by IR and 1H-NMR spectroscopy. The cleavage of aromatic azobond resulted in a potential colon-specific liberation of drug from conjugate studied in rat fecal contents. In vitro release profiles of polyphosphazene-linked conjugates of erlotinib have been studied at pH 1.2, pH 6.8 and pH 7.4. The stability study was designed to exhibit that free drug was released proficiently and unmodified from polyphosphazene-erlotinib conjugates having aromatic azo-bond in artificial colon conditions. Results: The synthesized conjugates were demonstrated to be stable in simulated upper gastro-intestinal tract conditions. The drug release kinetics shows that all the polymer-drug conjugates of erlotinib follow zero-order release kinetics which indicates that the drug release from the polymeric backbone is independent of its concentration. Kinetic study of conjugates with slope (n) shows the anomalous type of release with an exponent (n) > 0.89 indicating a super case II type of release. Conclusion: These studies indicate that polyphosphazene linked drug conjugates of erlotinib could be the promising candidates for the site-specific treatment of colon cancer with least detrimental side-effects.

Download Full-text

Doxorubicin Embedded into Nanofibrillated Bacterial Cellulose (NFBC) Produces a Promising Therapeutic Outcome for Peritoneally Metastatic Gastric Cancer in Mice Models via Intraperitoneal Direct Injection

Nanomaterials ◽

10.3390/nano11071697 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1697

Author(s):

Hidenori Ando ◽

Takashi Mochizuki ◽

Amr S. Abu Lila ◽

Shunsuke Akagi ◽

Kenji Tajima ◽

...

Keyword(s):

Gastric Cancer ◽

Drug Delivery ◽

Tumor Growth ◽

Bacterial Cellulose ◽

Anticancer Agents ◽

Intraperitoneal Administration ◽

In Vitro Release ◽

Xenograft Model ◽

Tumor Growth Inhibition

Natural materials such as bacterial cellulose are gaining interest for their use as drug-delivery vehicles. Herein, the utility of nanofibrillated bacterial cellulose (NFBC), which is produced by culturing a cellulose-producing bacterium (Gluconacetobacter intermedius NEDO-01) in a medium supplemented with carboxymethylcellulose (CMC) that is referred to as CM-NFBC, is described. Recently, we demonstrated that intraperitoneal administration of paclitaxel (PTX)-containing CM-NFBC efficiently suppressed tumor growth in a peritoneally disseminated cancer xenograft model. In this study, to confirm the applicability of NFBC in cancer therapy, a chemotherapeutic agent, doxorubicin (DXR), embedded into CM-NFBC, was examined for its efficiency to treat a peritoneally disseminated gastric cancer via intraperitoneal administration. DXR was efficiently embedded into CM-NFBC (DXR/CM-NFBC). In an in vitro release experiment, 79.5% of DXR was released linearly into the peritoneal wash fluid over a period of 24 h. In the peritoneally disseminated gastric cancer xenograft model, intraperitoneal administration of DXR/CM-NFBC induced superior tumor growth inhibition (TGI = 85.5%) by day 35 post-tumor inoculation, compared to free DXR (TGI = 62.4%). In addition, compared with free DXR, the severe side effects that cause body weight loss were lessened via treatment with DXR/CM-NFBC. These results support the feasibility of CM-NFBC as a drug-delivery vehicle for various anticancer agents. This approach may lead to improved therapeutic outcomes for the treatment of intraperitoneally disseminated cancers.

Download Full-text

Formulation and Evaluation of Transdermal patch of Methimazole

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00811 ◽

2021 ◽

pp. 4667-4672

Author(s):

Nani Tadhi ◽

Himansu Chopra ◽

Gyanendra Kumar Sharma

Keyword(s):

Drug Release ◽

Release Kinetics ◽

In Vitro Release ◽

Transdermal Patch ◽

Formulation Development ◽

In Vitro Drug Release ◽

Drug Release Study ◽

Percent Moisture ◽

Release Study

Transdermal patch is a drug delivery device in which the drugs are incorporated and is design in such a way that it releases the drug in sustained and at predetermined rate to deliver the drug through the skin to the systemic circulation painlessly. The aim of this research study was to formulate a controlled and sustained release transdermal matrix type patch of Methimazole. The matrix patch was prepared by solvent casting method using a various polymer in different concentration, HPMC (hydrophilic), Eudragit RL100 and Ethyl cellulose (hydrophobic) polymer. Total 9 prototype formulation were prepared and it was subjected for various evaluation test; weight uniformity, Folding endurance, thickness, Drug content, percent moisture content, percent Moisture uptake and In-vitro drug release study using Franz diffusion cell. The in-vitro CDR% data was fit into kinetics model to see the release kinetics from the patches. The Formulation F5 was choosen as a best formulation according to in-vitro drug release study. The in-vitro release was found 81.12 % in 12 hours, it followed zero order kinetics. The nature of polymer and concentration ratio of polymers plays a crucial role for obtaining a good transdermal patch design; therefore optimisation is very important step to formulate a desired TDDS. Therefore the result of the study encourages a further study and is hopeful that the present study would contribute to the recent pharmaceutical research for formulation development.

Download Full-text

Fabrication and Release Kinetics of Liposomes Containing Leuprolide Acetate

Journal of Basic and Applied Research in Biomedicine ◽

10.51152/jbarbiomed.v7i1.213 ◽

2021 ◽

Vol 7 (1) ◽

pp. 35-38

Author(s):

Sudipta Das ◽

Arnab Samanta ◽

Koushik Bankura ◽

Debatri Roy ◽

Amit Nayak

Keyword(s):

Drug Release ◽

Release Kinetics ◽

In Vitro Release ◽

Zero Order ◽

Leuprolide Acetate ◽

Lipid Film ◽

In Vitro Drug Release ◽

Liposomal Formulations ◽

Kinetics Of

The present work is focused on the preparation and in vitro release kinetics of liposomal formulation of Leuprolide Acetate. In this work, “Thin Lipid Film Hydration Method” was used for preparation of Leuprolide Acetate loaded liposomes. Prepared liposomal formulations of Leuprolide acetate was evaluated by drug entrapment study, in-vitro drug release kinetics and stability studies. The percentage drug entrapment of Leuprolide acetate for F1 and F2 formulations were found to be 78.14 ± 0.67 and 66.70 ± 0.81% respectively. In-vitro drug release study of liposomal formulations had shown zero order release pattern. Regression co-efficient (R2) value of Zero order kinetics for F1 and F2 formulations were 0.9912 and 0.9676 respectively. After storing formulations for 1 month, stability testing was done at 40C.It was found that all batches were stable. These liposomal formulations of Leuprolide acetate can be formulated for parenteral application to treat prostate cancer and in women, to treat symptoms of endometriosis (overgrowth of uterine lining outside of the uterus) or uterine fibroids.

Download Full-text

In vitro Release Kinetics Study of Ranolazine from Swellable Hydrophilic Matrix Tablets

Dhaka University Journal of Pharmaceutical Sciences ◽

10.3329/dujps.v8i1.5333 ◽

1970 ◽

Vol 8 (1) ◽

pp. 31-38 ◽

Cited By ~ 1

Author(s):

Mohammad Nezab Uddin ◽

Ishtiaq Ahmed ◽

Monzurul Amin Roni ◽

Muhammad Rashedul Islam ◽

Mohammad Habibur Rahman ◽

...

Keyword(s):

Drug Release ◽

Sustained Release ◽

Release Kinetics ◽

In Vitro Release ◽

High Viscosity ◽

Matrix Tablets ◽

Release Studies ◽

The Matrix ◽

Vitro Release

The objective of this study was to design oral sustained release matrix tablets of Ranolazine usinghydroxypropyl methylcellulose (HPMC) as the retardant polymer and to study the effect of formulation factors suchas polymer proportion and polymer viscosity on the release of drug. In vitro release studies were performed usingUSP type II apparatus (paddle method) in 900 mL of 0.1N HCl at 100 rpm for 12 hours. The release kinetics wasanalyzed using the zero-order, first order, Higuchi and Korsmeyer-Peppas equations to explore and explain themechanism of drug release from the matrix tablets. In vitro release studies revealed that the release rate decreasedwith increase in polymer proportion and viscosity grade. Mathematical analysis of the release kinetics indicated thatthe nature of drug release from the matrix tablets was dependent on drug diffusion and polymer relaxation andtherefore followed non-Fickian or anomalous release. The developed controlled release matrix tablets of Ranolazineprepared with high viscosity HPMC extended release up to 12 hours.Key words: Ranolazine; Sustained release; Methocel E50 Premium LV; Methocel K100LV CR; Methocel K4M CR;Methocel K15M CR.DOI: 10.3329/dujps.v8i1.5333Dhaka Univ. J. Pharm. Sci. 8(1): 31-38, 2009 (June)

Download Full-text

COMPARATIVE EVALUATION OF SELECTED POLYMERS AND PLASTICIZER ON TRANSDERMAL DRUG DELIVERY SYSTEM

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i1.21960 ◽

2018 ◽

Vol 10 (1) ◽

pp. 67

Author(s):

Bhawana Sethi ◽

Rupa Mazumder

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Propylene Glycol ◽

Drug Delivery System ◽

Transdermal Drug Delivery ◽

Release Kinetics ◽

Content Uniformity ◽

Transdermal Drug Delivery System ◽

Transdermal Patches

Objective: The present work was aimed at preparation of transdermal patches by a solvent casting method using a varying concentration of polymers i.e. methocel (K15 and K100), ethocel (4 and 10), gelatin, chitosan, eudragit (RL and RS) grade using plasticizer (glycerin and propylene glycol).Methods: The ratio of drug to polymers and plasticizer was varied and the effect of formulation variables was studied. Prepared transdermal patches were evaluated for physicochemical properties, in-vitro permeation studies, content uniformity, primary skin irritation studies and FT-IR studies.Results: The formulated transdermal patch by using Methocel K 100 M showed good physical properties. The average weight of patches prepared using glycerin as a plasticizer were ranged from 42.33-67.00 mg and propylene glycol as a plasticizer were ranged from 40.67-67.67 mg. The percentage moisture absorption varies from 1.76 to 10.73 for patches formulated using glycerin and 2.28 to 7.97 for propylene glycol patches. The percentage moisture loss from patches prepared using glycerin was ranged from 2.75 to 11.54 and 2.87 to 12.02 from propylene glycol. The water vapour transmission rate from patches prepared using glycerin was ranged from 0.25 to 0.92 and 0.41 to 1.76. The formulated patch showed the acceptable quantity of medicament ranged from (100.20-101.05%). This result met the test content uniformity as per BP (85% to 115%). According to that, the drug was consistent throughout the patches. The formulation PGD is considered as the best formulation, since it shows a maximum in vitro drug release as 43.75 % at 24 h. The drug release kinetics studied showed that the majority of formulations was following zero order.Conclusion: In conclusion, controlled release transdermal drug delivery system patches of aliskiren can be prepared using polymer combinations, with a different plasticizer. The release rate of drug depends upon the polymer. However, release kinetics followed zero order.

Download Full-text

DESIGN AND IN VITRO/IN VIVO EVALUATION OF EXTENDED RELEASE MATRIX TABLETS OF NATEGLINIDE

Journal of Biomedical and Pharmaceutical Research ◽

10.32553/jbpr.v7i6.559 ◽

2018 ◽

Vol 7 (6) ◽

Author(s):

Mohini Sihare ◽

Rajendra Chouksey

Keyword(s):

Drug Release ◽

Release Kinetics ◽

In Vitro Release ◽

Release Profile ◽

Matrix Tablets ◽

In Vivo Studies ◽

Release Mechanism ◽

In Vivo Evaluation

Aim: Nateglinide is a quick acting anti-diabetic medication whose potent activity lasts for a short duration. One of the dangerous side effects of nateglinide administration is rapid hypoglycemia, a condition that needs to be monitored carefully to prevent unnecessary fatalities. The aim of the study was to develop a longer lasting and slower releasing formulation of nateglinide that could be administered just once daily. Methods: Matrix tablets of nateglinide were prepared in combination with the polymers hydroxypropylmethylcellulose (HPMC), eudragits, ethyl cellulose and polyethylene oxide and the formulated drug release patterns were evaluated using in vitro and in vivo studies. Conclusion: Of the seventeen formulated matrix tablets tested, only one formulation labelled HA-2 that contained 15% HPMC K4M demonstrated release profile we had aimed for. Further, swelling studies and scanning electron microscopic analysis confirmed the drug release mechanism of HA-2. The optimized formulation HA-2 was found to be stable at accelerated storage conditions for 3 months with respect to drug content and physical appearance. Mathematical analysis of the release kinetics of HA-2 indicated a coupling of diffusion and erosion mechanisms. In-vitro release studies and pharmacokinetic in vivo studies of HA-2 in rabbits confirmed the sustained drug release profile we had aimed for. Keywords: Hydroxypropylmethylcellulose, Matrix tablets, Nateglinide, Sustained release

Download Full-text

Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery

Polymers ◽

10.3390/polym11020369 ◽

2019 ◽

Vol 11 (2) ◽

pp. 369 ◽

Cited By ~ 14

Author(s):

Seok Park ◽

Min Kim ◽

Seung-Ki Baek ◽

Jung-Hwan Park ◽

Seong-O Choi

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Diffusion Barrier ◽

Structural Changes ◽

Tertiary Structure ◽

Ex Vivo ◽

Release Kinetics ◽

In Vitro Release ◽

Transdermal Drug Delivery System ◽

Initial Burst

In this study we present polymeric microneedles composed of multiple layers to control drug release kinetics. Layered microneedles were fabricated by spraying poly(lactic-co-glycolic acid) (PLGA) and polyvinylpyrrolidone (PVP) in sequence, and were characterized by mechanical testing and ex vivo skin insertion tests. The compression test demonstrated that no noticeable layer separation occurred, indicating good adhesion between PLGA and PVP layers. Histological examination confirmed that the microneedles were successfully inserted into the skin and indicated biphasic release of dyes incorporated within microneedle matrices. Structural changes of a model protein drug, bovine serum albumin (BSA), in PLGA and PVP matrices were examined by circular dichroism (CD) and fluorescence spectroscopy. The results showed that the tertiary structure of BSA was well maintained in both PLGA and PVP layers while the secondary structures were slightly changed during microneedle fabrication. In vitro release studies showed that over 60% of BSA in the PLGA layer was released within 1 h, followed by continuous slow release over the course of the experiments (7 days), while BSA in the PVP layer was completely released within 0.5 h. The initial burst of BSA from PLGA was further controlled by depositing a blank PLGA layer prior to forming the PLGA layer containing BSA. The blank PLGA layer acted as a diffusion barrier, resulting in a reduced initial burst. The formation of the PLGA diffusion barrier was visualized using confocal microscopy. Our results suggest that the spray-formed multilayer microneedles could be an attractive transdermal drug delivery system that is capable of modulating a drug release profile.

Download Full-text

SODIUM ALGINATE/GELATIN MICROBEADS-INTERCALATED WITH KAOLIN NANOCLAY FOR EMERGING DRUG DELIVERY IN WILSON’S DISEASE

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019v11i5.34254 ◽

2019 ◽

pp. 71-80 ◽

Cited By ~ 2

Author(s):

O. SREEKANTH REDDY ◽

M. C. S. SUBHA ◽

T. JITHENDRA ◽

C. MADHAVI ◽

K. CHOWDOJI RAO ◽

...

Keyword(s):

Electron Microscopy ◽

Scanning Electron Microscopy ◽

Drug Release ◽

Ftir Spectroscopy ◽

Sodium Alginate ◽

Release Kinetics ◽

In Vitro Release ◽

Vitro Release ◽

Scanning Electron

Objective: The aim of the present study was to fabricate and evaluate the drug release studies using Sodium Alginate (SA) and Gelatin (GE) microbeads intercalated with Kaolin (KA) nanoclay for sustained release of D-Penicillamine (D-PA). Methods: Sodium alginate/gelatin/Kaolin blend microbeads were prepared by an extrusion method by using glutaraldehyde (GA) as a crosslinker. The obtained microbeads were characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and X–ray diffraction (XRD). Drug release kinetics of the microbeads was investigated in simulated intestinal fluid (pH 7.4) at 37 °C. Results: Microbeads formation was confirmed by FTIR spectroscopy. X-RD reveals that the KA should be intercalated with the drug and also it confirms the molecular level dispersion of D-Penicillamine into microbeads. Scanning Electron Microscopy (SEM) studies reveal that the beads were in spherical shape with some wrinkled depressions on the surface. The in vitro release study indicates the D-Penicillamine released in a controlled manner. The in vitro release kinetics was assessed by Korsmeyer-Peppas equation and the ‘n’ value lies in between 0.557-0.693 indicates Non-Fickian diffusion process. Conclusion: The results suggest that the developed KA intercalated microbeads are good potential drug carrier for the controlled release of D-PA.

Download Full-text