In Vitro and In Vivo Evaluation of 3D Printed Capsules with Pressure Triggered Release Mechanism for Oral Peptide Delivery

Rebamipide, an amino acid derivative of 2-(1H)-quinolinone, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. The current research study aimed to develop novel gastro-retentive mucoadhesive microspheres of rebamipide using ionotropic gelation technique. Studies of micromeritic properties confirmed that microspheres were free flowing with good packability. The in vitro drug release showed the sustained release of rebamipide up to 99.23 ± 0.13% within 12 h whereas marketed product displayed the drug release of 95.15 ± 0.23% within 1 h. The release mechanism from microspheres followed the zero-order and Korsmeyer-Peppas (R2 = 0.915, 0.969), respectively. The optimized M12 formulation displayed optimum features, such as entrapment efficiency 97%, particle size 61.94 ± 0.11 µm, percentage yield 98%, swelling index 95% and mucoadhesiveness was 97%. FTIR studies revealed no major incompatibility between drug and excipients. SEM confirmed the particles were of spherical in shape. Optimized formulation (M12) were stable at 40°C ± 2°C/75% RH ± 5% RH for 6 months. In vivo studies were performed and kinetic parameters like Cmax, Tmax, AUC0-t, AUC0-∞, t1/2, and Kel were calculated. The marketed product Cmax (3.15 ± 0.05 ng/mL) was higher than optimized formulation (2.58 ± 0.03 ng/mL). The optimized formulation AUC0-t (15.25 ± 1.14 ng.hr/mL), AUC0-∞ (19.42 ± 1.24 ng.hr/mL) was significantly higher than that of marketed product AUC0-t (10.21 ± 1.26 ng.hr/mL) and AUC0-∞ (13.15 ± 0.05 ng.hr/mL). These results indicate an optimized formulation bioavailability of 2.5-fold greater than marketed product.

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

Tailored on demand anti-coagulant dosing: An in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms

European Journal of Pharmaceutics and Biopharmaceutics ◽

10.1016/j.ejpb.2018.04.010 ◽

2018 ◽

Vol 128 ◽

pp. 282-289 ◽

Cited By ~ 34

Author(s):

Basel Arafat ◽

Nidal Qinna ◽

Milena Cieszynska ◽

Robert T. Forbes ◽

Mohamed A. Alhnan

Keyword(s):

Dosage Forms ◽

Oral Dosage ◽

In Vivo Evaluation ◽

On Demand ◽

3D Printed ◽

Oral Dosage Forms

Download Full-text

Chitosan Nanocapsules as Carriers for Oral Peptide Delivery: Effect of Chitosan Molecular Weight and Type of Salt on the In Vitro Behaviour and In Vivo Effectiveness

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2006.429 ◽

2006 ◽

Vol 6 (9) ◽

pp. 2921-2928 ◽

Cited By ~ 39

Author(s):

C. Prego ◽

D. Torres ◽

M. J. Alonso

Keyword(s):

Molecular Weight ◽

Salmon Calcitonin ◽

Peptide Delivery ◽

Oral Peptide Delivery ◽

Chitosan Hydrochloride ◽

Solvent Displacement ◽

Dose Dependent ◽

Chitosan Salt

We have recently reported preliminary data showing the efficacy of chitosan nanocapsules as carriers for oral peptide delivery. In the present work, our aim was to investigate the influence of some chitosan properties, such as the molecular weight and type of salt, on the interaction of these nanocapsules with the Caco-2 cells and also on their in vivo effectiveness. Chitosan nanocapsules were prepared by the solvent displacement technique using high (450 kDa) and medium (160 kDa) molecular weight chitosan glutamate as well as high molecular weight chitosan hydrochloride (270 kDa). The results indicated that the size of the nanocapsules was dependent on the chitosan molecular weight, whereas the zeta potential and the association efficiency of salmon calcitonin were not affected by the chitosan properties. Upon incubation with the Caco-2 cells, chitosan nanocapsules exhibited a dose-dependent cellular viability, which was hardly affected by, either the chitosan molecular weight or, the type of salt. In addition, it was observed that the transepithelial electrical resistance of the Caco-2 monolayer was not significantly modified upon their exposure to chitosan nanocapsules. The results of the in vivo studies, following oral administration to rats, indicated that chitosan nanocapsules were able to reduce significantly the serum calcium levels, and to prolong this reduction for at least 24 hours, irrespective of the type of chitosan salt and molecular weight of chitosan. Consequently, the performance of chitosan nanocapsules as oral carriers for salmon calcitonin was not affected by the characteristics of chitosan.

Download Full-text

3D printed extended release tablets for once daily use: An in vitro and in vivo evaluation study for a personalized solid dosage form

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2021.120222 ◽

2021 ◽

Vol 596 ◽

pp. 120222

Author(s):

Hazal Ezgi Gültekin ◽

Serdar Tort ◽

Fatmanur Tuğcu-Demiröz ◽

Füsun Acartürk

Keyword(s):

Dosage Form ◽

Extended Release ◽

Evaluation Study ◽

In Vivo Evaluation ◽

Once Daily ◽

Solid Dosage Form ◽

Solid Dosage ◽

3D Printed

Download Full-text

Gastroretentive Floating-Bioadhesive Drug Delivery System for Rebamipide: Design, In vitro and In vivo Evaluation

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2019.12.3.4 ◽

2019 ◽

Vol 12 (3) ◽

pp. 4534-4543

Author(s):

Ramarao Ajmeera ◽

Rajesh Gollapudi

Keyword(s):

Immediate Release ◽

Relative Bioavailability ◽

Fickian Diffusion ◽

Release Mechanism ◽

In Vivo Evaluation ◽

Healthy Human ◽

Weight Variation ◽

Significant Difference

Rebamipide is an amino acid analog of 2-(1H)-quinolinone used in the treatment of peptic ulcer. Here we sought to formulate and evaluate gastroretentive floating-bioadhesive tablets of rebamipide to increase the gastric residence time and further compare their pharmacokinetics with conventional immediate release tablets. Floating-bioadhesive tablets of rebamipide were prepared with combination of Polyox WSR 303 and CP 971P/HPMC K4M and Sodium CMC by direct compression method. The prepared formulations were evaluated for hardness, thickness, weight variation, friability, drug content, in vitro buoyancy and drug release. The optimized formulation (RBF12) floated with a lag time of 28.3 ± 3.2 sec, duration of floating 12 h and released about 99.91 ± 1.84% of drug in 12 h, and then followed non-Fickian diffusion release mechanism with n value of 0.635. The RBF12 tablets with BaSO4 remained in stomach for 5.13 ± 0.64 h (n=3) in radiological studies. The formulation, RBF12 exhibited maximum bioadhesive strength (1.346 ± 0.110 N) than other formulations. The bioavailability studies were carried out for the optimized formulation (RBF12) and compared with that of reference IR tablets “Rebagen” in nine healthy human volunteers. Based on in vivo performance significant difference was observed between Cmax, tmax, t1/2, AUC0–∞, and MRT of RBF12 and IR tablets. The increase in relative bioavailability of RBF12 was 1.7-fold when compared to reference IR tablets. The increased relative oral bioavailability may be due to the floating-bioadhesive mechanism of dosage form, which is desirable for drugs absorbed from the upper part of gastrointestinal tract.

Download Full-text