scholarly journals Sustained Release of Protein Therapeutics from Subcutaneous Thermosensitive Biocompatible and Biodegradable Pentablock Copolymers (PTSgels)

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Elizabeth Schaefer ◽  
Santhi Abbaraju ◽  
Mary Walsh ◽  
Donna Newman ◽  
Jacklyn Salmon ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Drug Release ◽  
Sustained Release ◽  
Near Infrared ◽  
Structural Integrity ◽  
Polymer Composition ◽  
Sds Page ◽  
Pentablock Copolymers

Objective. To evaluate thermosensitive, biodegradable pentablock copolymers (PTSgel) for sustained release and integrity of a therapeutic protein when injected subcutaneously. Materials and Methods. Five PTSgels with PEG-PCL-PLA-PCL-PEG block arrangements were synthesized. In vitro release of IgG from PTSgels and concentrations was evaluated at 37°C. Released IgG integrity was characterized by SDS-PAGE. In vitro disintegration for 10GH PTSgel in PBS was monitored at 37°C over 72 days using gravimetric loss and GPC analysis. Near-infrared IgG in PTSgel was injected subcutaneously and examined by in vivo imaging and histopathology for up to 42 days. Results. IgG release was modulated from approximately 7 days to more than 63 days in both in vitro and in vivo testing by varying polymer composition, concentration of PTSgel aqueous solution, and concentration of IgG. Released IgG in vitro maintained structural integrity by SDS-PAGE. Subcutaneous PTSgels were highly biocompatible and in vitro IgG release occurred in parallel with the disappearance of subcutaneous gel in vivo. Conclusions. Modulation of release of biologics to fit the therapeutic need can be achieved by varying the biocompatible and biodegradable PTSgel composition. Release of IgG parallels disappearance of the polymeric gel; hence, little or no PTSgel remains after drug release is complete.

scholarly journals Development and In Vitro-In Vivo Evaluation of a Novel Sustained-Release Loxoprofen Pellet with Double Coating Layer

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 260 ◽  
Author(s):  
Dongwei Wan ◽  
Min Zhao ◽  
Jingjing Zhang ◽  
Libiao Luan
Keyword(s):  
Citric Acid ◽  
Drug Release ◽  
Sustained Release ◽  
Release Rate ◽  
Diffusion Rate ◽  
Immediate Release ◽  
Pharmacokinetic Studies ◽  
Release Tablet

This study aimed to develop a novel sustained release pellet of loxoprofen sodium (LXP) by coating a dissolution-rate controlling sub-layer containing hydroxypropyl methyl cellulose (HPMC) and citric acid, and a second diffusion-rate controlling layer containing aqueous dispersion of ethyl cellulose (ADEC) on the surface of a LXP conventional pellet, and to compare its performance in vivo with an immediate release tablet (Loxinon®). A three-level, three-factor Box-Behnken design and the response surface model (RSM) were used to investigate and optimize the effects of the citric acid content in the sub-layer, the sub-layer coating level, and the outer ADEC coating level on the in vitro release profiles of LXP sustained release pellets. The pharmacokinetic studies of the optimal sustained release pellets were performed in fasted beagle dogs using an immediate release tablet as a reference. The results illustrated that both the citric acid (CA) and ADEC as the dissolution- and diffusion-rate controlling materials significantly decreased the drug release rate. The optimal formulation showed a pH-independent drug release in media at pH above 4.5 and a slightly slow release in acid medium. The pharmacokinetic studies revealed that a more stable and prolonged plasma drug concentration profile of the optimal pellets was achieved, with a relative bioavaibility of 87.16% compared with the conventional tablets. This article provided a novel concept of two-step control of the release rate of LXP, which showed a sustained release both in vitro and in vivo.

scholarly journals Non-invasive, real-time reporting drug release in vitro and in vivo

2015 ◽  
Vol 51 (32) ◽  
pp. 6948-6951 ◽  
Author(s):  
Yanfeng Zhang ◽  
Qian Yin ◽  
Jonathan Yen ◽  
Joanne Li ◽  
Hanze Ying ◽  
...  
Keyword(s):  
Drug Release ◽  
Real Time ◽  
Near Infrared ◽  
Reporting System ◽  
Real Time Monitoring ◽  
Near Infrared Fluorescence ◽  
Non Invasive ◽  
Fluorescence Dye

Anin vitroandin vivodrug-reporting system is developed for real-time monitoring of drug release via the analysis of the concurrently released near-infrared fluorescence dye.

In-Vitro Functionality of Clozapine Biphasic Release Minitablet Using Advanced Statistical Tools

2021 ◽  
Vol 11 ◽  
Author(s):  
Hardik Rana ◽  
Rushikesh Chaudhari ◽  
Vaishali Thakkar ◽  
Tejal Gandhi
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Ethyl Cellulose ◽  
Dosage Form ◽  
Immediate Release ◽  
Solid Dosage Form ◽  
Solid Dosage ◽  
Precipitation Inhibitor

Background: The better control of the drug release with immediate effect is the major concern to achieve better therapeutic action and patient compliance. The failure of the solid dispersion complex during storage as well as in-vivo is another concern for the oral solid dosage form. Objective: The prime objective of the present study was to optimize the biphasic minitablet incorporating quality by design approach using the combination of waxy erodible and water-impermeable excipients. Exploration of Soluplus as a precipitation inhibitor and Dexolve as a solubility enhancer in oral solid dosage form was the secondary objective. Methods: The drug-Excipient compatibility study was assessed by FTIR. Clozapine was chosen as a model drug that has poor aqueous solubility. The complex was formulated using B-cyclodextrin or HP B-CD or Dexolve by kneading method. The screening of solubility enhancers and their amount were performed based on phase solubility study. The precipitation inhibitor was screened as per the parachute effect study. Immediate release minitablets were formulated using a direct compression method using different disintegrating agents. The IR minitablets were evaluated for different evaluation parameters. The sustained release minitablets was formulated by hot-melt granulation technique incorporating the Precirol ATO 5 as a waxy excipient and ethyl cellulose as water impermeable excipient. The SR minitablet was optimized using a central composite design. The amount of Precirol ATO 5 and ethyl cellulose were chosen as independent variables and % drug release at 1, 6, and 10 h was selected as responses. The designed batches were evaluated for different pre and post compressional parameters. The IR and SR minitablets were filled in a capsule as per dose requirement and evaluated for in-vitro drug release. The in-vivo plasma concentration was predicted using the Back calculation of the Wagner – Nelson approach. Results: Drug – Excipient study revealed that no significant interaction was observed. Dexolve was screened as a solubility enhancer for the improvement of the solubility of clozapine. The Soluplus was chosen as a precipitation inhibitor from the parachute effect study. The immediate-release tablet was formulated using Prosolv EASYtab SP yield less disintegration time with better flowability. The sustained release mini-tablet was formulated using Precirol ATO 5 and ethyl cellulose. Two-dimensional and three-dimensional plots were revealed the significant effect of the amount of Precirol ATO 5 and ethyl cellulose. The overlay plot locates the optimized region. The in-vitro drug release study revealed the desired drug release of the final combined formulation. The in-vivo plasma concentration-time confirms the drug release up to 12h. Conclusion: The biphasic mini-tablets were formulated successfully for better control of drug release leads to high patient compliance. The use of soluplus as a precipitation inhibitor is explored in the oral solid dosage form for a poorly aqueous drug. Prosolv EASYtab SP was incorporated in the formulation as super disintegrant. The amount of Precirol ATO 5 and ethyl cellulose had a significant effect on drug release in sustained-release minitablet. The approach can be useful in the industry.

scholarly journals FORMUALTION AND DEVELOPMENT OF MUCOADHESIVE SUSTAINED RELEASE BUCCAL TABLETS AND PATCHES OF 5-FLUOROURACIL USING DIFFERENT POLYMERS

2018 ◽  
Vol 11 (5) ◽  
pp. 174
Author(s):  
Nitin Gawai ◽  
Zahid Zaheer
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Research Work ◽  
Sodium Deoxycholate ◽  
Content Uniformity ◽  
Design Expert ◽  
Buccal Tablet ◽  
Buccal Tablets

 Objective: The present research study was undertaken to formulate mucoadhesive sustained release buccal tablets and patches of 5-fluorouracil (5-FU).Method: For the research experiment work design expert software version 10, stat-ease, Inc. has been used. A 32 full factorial design was selected for the formulation of the buccal tablet as well as buccal patches. In this research work, formulated tablets and patches using different polymers such as carbopol 974p, polyvinylpyrrolidone-K 30, sodium deoxycholate, microcrystalline cellulose, and polyvinyl alcohol. An after formulation of batches formulated products studied for characterization, namely, Fourier transform infrared (FTIR) and differential scanning calorimeter (DSC). Evaluation parameters studied such as weight uniformity, thickness, hardness, friability, and content uniformity also carried out. For drug release purpose from the formulation of buccal tablet and patches in vitro drug released performed. In vivo drug releases study also carried out using Rabbit for drug reaction point of view.Results: Design expert showed the significant results on independent and dependent variables. The R-Squared 0.9943 for drug release and 0.9985 for swelling index is in reasonable agreement with the formulations. FTIR and DSC indicating compatibility of the drug and polymers in the tablet formulation and patch formulations at the molecular level. The drug release of buccal tablet showed 75.10–99.34% and buccal patches showed 58.41–81.43%. These formulations showed good results when compared to the conventional tablet.Conclusion: Formulation of mucoadhesive sustained release buccal tablets and patches of 5-FU successfully done using different polymers, which would definitely help in increasing bioavailability of the drug.

scholarly journals Formulation and Evaluation of Meloxicam In-Situ Gel Designed for Sustained Drug Release to Reduce Dosing Frequency in the Management of Arthritis

2021 ◽  
Vol 69 (2) ◽  
Author(s):  
Meesala. Srinivasa Rao ◽  
M. S Chandra Goud ◽  
C. V. Reddy
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Sustained Drug Release ◽  
In Vitro Drug Release ◽  
In Situ Gel ◽  
Dosing Frequency ◽  
Gel Formulations

Meloxicam has short biological half-life and is rapidly eliminated, frequent oral administration is necessary to maintain its therapeutic concentration, but this can increase chances of missing dose. This makes Meloxicam a good applicant for oral sustained release formulation. The objective of study was to develop in-situ gel formulations of Meloxicam for sustained release to reduce the dosing frequency in the treatment of rheumatoid arthritis. Method of Ion sensitive in-situ gelation was used in this study. Meloxicam In-situ gel formulations were prepared by varying concentrations of sodium alginate as a bio-degradable gel forming polymer, CaCl2 as a cross-linking agent and Chitosan/ HPMCK4/HPMCK15/Guar gum/Gellan gum/ Xantha gum/pectin were used as drug release rate controlling polymers. The formulations F11-F18 were assessed for Physical appearance, pH, in-vitro drug release, viscosity, in-vitro gelling capacity and drug content. FTIR, DSC and in-vivo drug kinetics studies was conducted for Meloxicam, excipients used and optimized formulation. Formulations showed an optimum viscosity that will allow ease of administration and swallowing. All formulations are shown pH between4.7-4.9, floating lag time was 2-3sec and floated for >12 hrs. In vitro drug release studies reporting that commercially available product Meloxicam SR has showed 99.92% drug release in 8 hrs and out of eight formulations F11 showing in-vitro drug release of 99.52% over a 12hrs extended period. FTIR studies revealed no interaction between drug and excipients used. The results of In-vivo kinetic studies are approving the better performance of the optimized formulation in comparison to marketed formulation, The Cmax, Tmax, half-life AUC values are confirming the same thing. In conclusion, Formulation (F11) was selected as optimized formulations could be offered as shows optimum sustained drug release compared to commercial formulation. Hence Meloxicam containing Chitosan as drug release controll

Design and in vivo Evaluation of Gastro-retentive Floating Capsules of Amlodipine Besylate in Healthy Human Volunteers

2017 ◽  
Vol 10 (6) ◽  
pp. 3891-3899
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Chenna Madipalli Shalina ◽  
Vishnu Pulavarthy ◽  
Viswaja Medipally
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Sustained Release ◽  
In Vivo Studies ◽  
Amlodipine Besylate ◽  
In Vivo Evaluation ◽  
Healthy Human ◽  
Gastro Retentive

The aim of this study was to explore the application of Gelucire 43/01 for the design of sustained release gastro retentive drug delivery system of Amlodipine besylate. Gelucire 43/01 has been used in floating sustained release formulations to prolong gastric residence time and increase its bioavailability. Gelucire 43/01 in combination with HPMC and Polyox was used as a release retarding polymer. HPMC of various viscosity grades HPMC K4M, HPMC K15M and HPMC K100M in combination of Gelucire were tested to obtain optimal total floating time as well as controlled drug release for prolonged period. Melt granulation technique has been used to prepare gastro retentive Amlodipine besylate formulations. All the formulations were evaluated in vitro for their floating ability and drug release. The floating times of all tablet formulations were greater than 12h. HPMC K4M in combination with Gelucire as polymeric matrix enhanced the drug release due to addition of hydrophilic polymer facilitated the swelling and erosion of the tablets. Incorporation of low viscosity polymer HPMC K100 M resulted in optimal floating as well as drug release for longer time. In vivo studies of optimized formulation show floating ability for 6 h in stomach. The results indicate that Gelucire 43/01 in combination with dissolution enhancers HPMC increase the permeability of the wax matrix, which provides improved dissolution thereby bioavailability of Amlodipine besylate and can be considered as a carrier for the development of sustained release floating drug delivery systems.  

scholarly journals In Vitro and In Vivo Evaluation of pH-Sensitive Hydrogels of Carboxymethyl Chitosan for Intestinal Delivery of Theophylline

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hemant Kumar Singh Yadav ◽  
H. G. Shivakumar
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Extended Release ◽  
Carboxymethyl Chitosan ◽  
Ph Sensitive ◽  
Acidic Ph ◽  
Release Formulation ◽  
Nocturnal Asthma

Chitosan is a natural polymer which has limited solubility. Chitosan gets solubilized at acidic pH but is insoluble at basic pH. In the present study, carboxymethyl chitosan (CMC) was prepared which shows high swelling in basic pH and thus can delay the drug release and can act as matrix for extended release formulation. CMC was characterized by FTIR and NMR. pH-sensitive hydrogels of theophylline were formulated using CMC and carbopol 934. Hydrogels were evaluated for swelling, drug content in vitro drug release studies, and in vivo studies on rabbit. The swelling studies have shown little swelling in acidic pH 432% at the end of two hours and 1631% in basic pH at the end of 12 hours. The release profile of the formulation I containing CMC and carbopol in 1 : 1 ratio showed sustained release. In vivo studies showed that the release of theophylline from the prepared hydrogel formulation (Test) exhibit better prolonged action when compared to (standard) marketed sustained release formulation. The studies showed that the pH-sensitive hydrogel of CMC can be used for extended release of theophylline in intestine and can be highly useful in treating symptoms of nocturnal asthma.

scholarly journals IN VITRO AND IN VIVO EVALUATION OF FLOATING GASTRORETENTIVE DRUG DELIVERY SYSTEM OF CIMETIDINE USING HARD ALGINATE CAPSULES

2018 ◽  
Vol 11 (6) ◽  
pp. 162
Author(s):  
Ririyen Dessy N Siahaan ◽  
Hakim Bangun ◽  
Sumaiyah Sumaiyah
Keyword(s):  
Drug Delivery ◽  
Gastric Mucosa ◽  
Drug Release ◽  
Sustained Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Release Profile ◽  
Alginate Capsules

Objective: The objective of this study was to evaluate in vitro and in vivo of gastroretentive drug delivery system of cimetidine using hard alginate capsules.Methods: Drug release study was tested to various hard alginate capsules containing 200 mg cimetidine with paddle method dissolution apparatus in artificial gastric fluid pH 1.2. Concentrations of cimetidine were measured using ultraviolet spectrophotometer at 218.4 nm wavelength. The product that fulfilled the sustained release profile was evaluated for bioavailability using male rabbits at dose 9.3 mg/kg orally, and the antiulcer studies were evaluated by HCl-induced ulcer method at cimetidine dose 18 mg/kg once a day orally. Gastric lesions were evaluated by macroscopic and microscopic observations.Results: The results of drug release test showed that hard alginate capsule made from sodium alginate 500–600 cP gave sustained release profile of cimetidine for 12 h. In vivo bioavailability studies showed that cimetidine given with hard alginate capsules gave higher of Cmax, Tmax, and area under the curve of cimetidine compared to cimetidine that given with conventional hard gelatin capsules. The antiulcer studies showed that the healing effect of cimetidine that given with hard alginate capsules was faster than cimetidine given in suspension form. Cimetidine that given with hard alginate capsules macroscopically showed no gastric lesion and histopathologically also showed normal gastric mucosa of rats after 4 days treatment. However, cimetidine given in suspension form showed of 0.036±0.024 ulcer index and microscopically there was still erosion of gastric mucosa of rats after 4 days treatment.Conclusion: Floating gastroretentive of cimetidine using hard alginate capsules give a sustained release of cimetidine with better bioavailability and antiulcer effect of cimetidine.

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