Fabrication of PLGA in situ Forming Implants and Study on Their Correlation of in vitro Release Profiles with in vivo Performances

2021 ◽  
pp. 1-11
Author(s):  
Song Yang ◽  
Mengya Hu ◽  
Wenqing Liu ◽  
Nuohan Hou ◽  
Kaidi Yin ◽  
...  
Keyword(s):  
In Vitro Release ◽  
In Situ Forming ◽  
Vitro Release ◽  
Release Profiles ◽  
In Situ Forming Implants

scholarly journals In Situ-Forming Microparticles for Controlled Release of Rivastigmine: In Vitro Optimization and In Vivo Evaluation

2021 ◽  
Vol 14 (1) ◽  
pp. 66
Author(s):  
Mohamed Haider ◽  
Ibrahim Elsayed ◽  
Iman S. Ahmed ◽  
Ahmed R. Fares
Keyword(s):  
Drug Release ◽  
In Vitro Release ◽  
Flip Flop ◽  
In Situ Forming ◽  
Internal Phase ◽  
The Matrix ◽  
Vitro Release

In this work, sucrose acetate isobutyrate (SAIB) and polylactic co-glycolic acid (PLGA) were used alone or in combination as a matrix-former (MF) to prepare long-acting injectable rivastigmine (RV) in situ-forming microparticles (ISM). RV-ISM were prepared by the emulsification of an internal phase, containing the drug and the matrix former(s), into an external oily phase containing a stabilizer. The statistical design, Central Composite Design (CCD), was adopted as a quality by design (QbD) approach to optimize the formulation of RV-ISM systems. The fabricated RV-ISM systems was designed to minimize the initial burst drug release and maximize the sustainment of RV release from the ISM and ease of injection. The influence of critical formulation variables such as the matrix-former to drug (MF/D) ratio and SAIB to PLGA (S/P) ratio in the internal phase with respect to critical quality attributes (CQAs), such as the percentage drug release within the first day (Q1), the time required for 50% drug release (T50%) and the rate of injection, were studied using the CCD. The optimal RV-ISM system with the highest desirability value (0.74) was predicted to have an MF/D ratio of 11.7:1 (w/w) and an S/P ratio of 1.64:1 (w/w). The optimal RV-ISM system was assessed for its release profile, injectability, rheological properties, morphology, effect on cell viability, tolerance to γ-sterilization and in vivo performance in male albino rabbits. In vitro release studies revealed that the optimal RV-ISM system released 100% of its drug content throughout a release period of 30 days with only 15.5% drug release within the first day (Q1) and T50% of 13.09 days. Moreover, the optimal system showed a high injection rate of 1.012 mL/min, pseudoplastic flow, uniform spherical globules with homogenous particle size, minimal cytotoxicity and high tolerability to γ-sterilization. In vivo pharmacokinetic (PK) studies revealed that the rate of absorption of RV from the optimal RV-ISM system was controlled compared to a drug solution following either intramuscular (IM) or subcutaneous (SC) injection. Furthermore, the optimal RV-ISM was found to follow flip-flop PK with poor correlation between in vitro release and in vivo findings. These findings suggest that the optimal RV-ISM is a promising tool to achieve a sustained release therapy for RV; however, further investigation is still required to optimize the in vivo performance of RV-ISM.

scholarly journals Preparation of a Sustained Release Drug Delivery System for Dexamethasone by a Thermosensitive, In Situ Forming Hydrogel for Use in Differentiation of Dental Pulp

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Elham Khodaverdi ◽  
Fatemeh Kheirandish ◽  
Farnaz Sadat Mirzazadeh Tekie ◽  
Bibi Zahra Khashyarmanesh ◽  
Farzin Hadizadeh ◽  
...  
Keyword(s):  
Phase Transition ◽  
Transition Temperature ◽  
Phase Transition Temperature ◽  
Delivery System ◽  
In Vitro Release ◽  
In Situ Forming ◽  
Release Study ◽  
Vitro Release

In situ forming delivery systems composed of block copolymers are attracting substantial attention due to their ease of use, biocompatibility, and biodegradability. In this study, the thermoresponsive triblock copolymer PLGA-PEG-PLGA was studied as a dexamethasone delivery system. Dexamethasone, a synthetic glucocorticoid, is used clinically to improve inflammation, pain, and the hyperemesis of chemotherapy, and it is applied experimentally as a differentiation factor in tissue engineering. PLGA-PEG-PLGA was synthesised under microwave irradiation for 5 min. The obtained copolymer was characterised to determine its structure and phase transition temperature. An in vitro release study was conducted for various copolymer structures and drug concentrations. The yield of the reaction and HNMR analysis confirmed the appropriateness of the microwave-assisted method for PLGA-PEG-PLGA synthesis. Phase transition temperature was affected by the drug molecule as well as by the copolymer concentration and structure. An in vitro release study demonstrated that release occurs mainly by diffusion and does not depend on the copolymer structure or dexamethasone concentration.

scholarly journals OPHTHALMIC IN-SITU SUSTAINED GEL OF CIPROFLOXACIN, PREPARATION AND EVALUATION STUDY

2018 ◽  
Vol 10 (4) ◽  
pp. 153 ◽  
Author(s):  
Fadia Yassir Al-bazzaz ◽  
Myasar Al-kotaji
Keyword(s):  
Hydroxypropyl Methylcellulose ◽  
In Vitro Release ◽  
Poloxamer 407 ◽  
Gelling Agent ◽  
In Situ Gel ◽  
Viscosity Modifier ◽  
Vitro Release

Objective: This work aims to formulate and evaluate an ophthalmic in-situ gel of ciprofloxacin hydrochloride (HCl) using poloxamer 407 (P407) as a gelling agent and hydroxypropyl methylcellulose (HPMC) as a viscosity modifier. The objective of this work was to prolong the contact time as the in-situ gel will be converted into a gel upon contact with the cul-de-sac. Methods: Ciprofloxacin HCl ophthalmic in-situ gel was prepared by utilizing (P407) as a temperature-dependent polymer while hydroxypropyl methylcellulose was used as a viscosity modifier. The system was evaluated for physical appearance, pH, drug content, sterility, irritancy and stability. In addition, gelation temperature and a viscosity at different shear rates and different temperatures were studied. The compatibility of the polymer with ciprofloxacin was studied by using fourier transform infrared spectroscopy (FTIR). The in vitro release of the drug was also evaluated and supported by a preliminary in vivo test.Results: The results showed that the prepared formulas were clear, with acceptable pH and the drug contents were within the acceptable limits. FTIR results detected no incompatibility between poloxamer 407 and ciprofloxacin HCl. Notably, the viscosity of the system showed a pseudoplastic behaviour where a reduction in viscosity upon increasing the shear rate was observed. The in vitro release study confirmed the prolongation of the release of the optimized formula (F6) up to 8 h. Upon application of F6 into eyes of rabbits there was no irritancy. In addition, in vivo elimination study showed a prolonged contact for the in-situ gel in comparison with the rapid clearance of eye drop. Stability study indicated the stability of the optimized formula (F6). Conclusion: The prepared optimized formula (F6) represents a successful, safe, stable and prolonged release in-situ gel formula of ciprofloxacin.

In-vitro Release Evaluation of Growth Hormone from an Injectable In-Situ Forming Gel Using PCL-PEG-PCL Thermosensitive Triblock

2020 ◽  
Vol 17 (2) ◽  
pp. 174-183
Author(s):  
Elham Khodaverdi ◽  
Khadijeh Delroba ◽  
Fatemeh Mohammadpour ◽  
Bahman Khameneh ◽  
Sayyed A. Sajadi Tabassi ◽  
...  
Keyword(s):  
Growth Hormone ◽  
In Vitro Release ◽  
Cd Spectrum ◽  
In Situ Forming ◽  
Sds Page ◽  
In Situ Forming Gel ◽  
The Stability ◽  
Vitro Release

Objective: An injectable long acting In-Situ Forming Gel (ISFG) of human Growth Hormone (hGH) was prepared by using triblock PCL-­‐PEG-­‐PCL (Mw 1500-1500-1500). Ring-Opening Polymerization (ROP) of triblock using microwave was applied. Methods: The BCA protein assay Kit was used to determine the concentration of hGH in the in-vitro release medium. Finally, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) tests and Circular Dichroism (CD) spectrum were done to approve the stability of released hGH. The result of ROP demonstrated that the proportion of PCL to PEG accorded with the initial molar ratio of the monomers. The cross-section of the Surface Electron Microscopy (SEM) indicated the porous framework of the hydrogel could load the drug into its tridimensional matrixes structure. There is the low initial burst release of hGH from the supramolecular hydrogel. Results: The maximum in-vitro release of hGH was 71.2 % ± 1.5 that were due to hGH degrading after this time (21 days). The CD spectrum and SDS-PAGE results confirmed the stability of hGH during invitro release evaluation. Conclusion: The results suggest that the sustained-release formulation using PCL-PEG-PCL can be applied to control the release of hGH.

scholarly journals In Vitro–In Vivo Correlation (IVIVC) Population Modeling for the In Silico Bioequivalence of a Long-Acting Release Formulation of Progesterone

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 255
Author(s):  
Elena M. Tosca ◽  
Maurizio Rocchetti ◽  
Elena Pérez ◽  
Conchi Nieto ◽  
Paolo Bettica ◽  
...  
Keyword(s):  
Clinical Studies ◽  
In Vitro Release ◽  
Release Formulation ◽  
Mixed Effect ◽  
Ring Model ◽  
Long Acting ◽  
Vitro Release ◽  
Release Profiles

Health authorities carefully evaluate any change in the batch manufacturing process of a drug before and after regulatory approval. In the absence of an adequate in vitro–in vivo correlation (Level A IVIVC), an in vivo bioequivalence (BE) study is frequently required, increasing the cost and time of drug development. This study focused on developing a Level A IVIVC for progesterone vaginal rings (PVRs), a dosage form designed for the continuous delivery in vivo. The pharmacokinetics (PK) of four batches of rings charged with 125, 375, 750 and 1500 mg of progesterone and characterized by different in vitro release rates were evaluated in two clinical studies. In vivo serum concentrations and in vitro release profiles were used to develop a population IVIVC progesterone ring (P-ring) model through a direct differential-equation-based method and a nonlinear-mixed-effect approach. The in vivo release, Rvivo(t), was predicted from the in vitro profile through a nonlinear relationship. Rvivo(t) was used as the input of a compartmental PK model describing the in vivo serum concentration dynamics of progesterone. The proposed IVIVC P-ring model was able to correctly predict the in vivo concentration–time profiles of progesterone starting from the in vitro PVR release profiles. Its internal and external predictability was carefully evaluated considering the FDA acceptance criteria for IVIVC assessment of extended-release oral drugs. Obtained results justified the use of the in vitro release testing in lieu of clinical studies for the BE assessment of any new PVRs batches. Finally, the possible use of the developed population IVIVC model as a simulator of virtual BE trials was explored through a case study.

Reliability of a Single β-Thromboglobulin Measurement in a Diabetic Population : Importance of PGE1 in Anticoagulant Mixture

1987 ◽  
Vol 57 (02) ◽  
pp. 201-204 ◽  
Author(s):  
P Y Scarabin ◽  
L Strain ◽  
C A Ludlam ◽  
J Jones ◽  
E M Kohner
Keyword(s):  
In Vitro Release ◽  
Mean Value ◽  
Reliable Estimate ◽  
Diabetic Patients ◽  
Single Measurement ◽  
Diabetic Population ◽  
The Difference ◽  
Vitro Release

SummaryDuring the collection of samples for plasma β-thromboglobulin (β-TG) determination, it is well established that artificially high values can be observed due to in-vitro release. To estimate the reliability of a single β-TG measurement, blood samples were collected simultaneously from both arms on two separate occasions in 56 diabetic patients selected for a clinical trial. From each arm, blood was taken into two tubes containing an anticoagulant mixture with (tube A) and without (tube B) PGE!. The overall mean value of B-TG in tube B was 1.14 times higher than in tube A (p <0.01). The markedly large between-arms variation accounted for the most part of within-subject variation in both tubes and was significantly greater in tube B than in tube A. Based on the difference between B-TG values from both arms, the number of subjects with artifically high B-TG values was significantly higher in tube B than in tube A on each occasion (overall rate: 28% and 14% respectively). Estimate of between-occasions variation showed that B-TG levels were relatively stable for each subject between two occasions in each tube. It is concluded that the use of PGEi decreases falsely high B-TG levels, but a single measurement of B-TG does not provide a reliable estimate of the true B-TG value in vivo.

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