scholarly journals Measuring dissolution profiles of single controlled-release drug pellets

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Heran C. Bhakta ◽  
Jessica M. Lin ◽  
William H. Grover
Keyword(s):  
Controlled Release ◽  
Resonance Frequency ◽  
Drug Product ◽  
The Body ◽  
Sensor Data ◽  
Drug Dissolution ◽  
Oral Drug ◽  
High Temporal Resolution ◽  
Drug Products

AbstractMany solid-dose oral drug products are engineered to release their active ingredients into the body at a certain rate. Techniques for measuring the dissolution or degradation of a drug product in vitro play a crucial role in predicting how a drug product will perform in vivo. However, existing techniques are often labor-intensive, time-consuming, irreproducible, require specialized analytical equipment, and provide only “snapshots” of drug dissolution every few minutes. These limitations make it difficult for pharmaceutical companies to obtain full dissolution profiles for drug products in a variety of different conditions, as recommended by the US Food and Drug Administration. Additionally, for drug dosage forms containing multiple controlled-release pellets, particles, beads, granules, etc. in a single capsule or tablet, measurements of the dissolution of the entire multi-particle capsule or tablet are incapable of detecting pellet-to-pellet variations in controlled release behavior. In this work, we demonstrate a simple and fully-automated technique for obtaining dissolution profiles from single controlled-release pellets. We accomplished this by inverting the drug dissolution problem: instead of measuring the increase in the concentration of drug compounds in the solution during dissolution (as is commonly done), we monitor the decrease in the buoyant mass of the solid controlled-release pellet as it dissolves. We weigh single controlled-release pellets in fluid using a vibrating tube sensor, a piece of glass tubing bent into a tuning-fork shape and filled with any desired fluid. An electronic circuit keeps the glass tube vibrating at its resonance frequency, which is inversely proportional to the mass of the tube and its contents. When a pellet flows through the tube, the resonance frequency briefly changes by an amount that is inversely proportional to the buoyant mass of the pellet. By passing the pellet back-and-forth through the vibrating tube sensor, we can monitor its mass as it degrades or dissolves, with high temporal resolution (measurements every few seconds) and mass resolution (700 nanogram resolution). As a proof-of-concept, we used this technique to measure the single-pellet dissolution profiles of several commercial controlled-release proton pump inhibitors in simulated stomach and intestinal contents, as well as comparing name-brand and generic formulations of the same drug. In each case, vibrating tube sensor data revealed significantly different dissolution profiles for the different drugs, and in some cases our method also revealed differences between different pellets from the same drug product. By measuring any controlled-release pellets, particles, beads, or granules in any physiologically-relevant environment in a fully-automated fashion, this method can augment and potentially replace current dissolution tests and support product development and quality assurance in the pharmaceutical industry.

scholarly journals Leveraging Oral Drug Development to a Next Level: Impact of the IMI-Funded OrBiTo Project on Patient Healthcare

2021 ◽  
Vol 8 ◽  
Author(s):  
Bart Hens ◽  
Patrick Augustijns ◽  
Hans Lennernäs ◽  
Mark McAllister ◽  
Bertil Abrahamsson
Keyword(s):  
Drug Development ◽  
In Silico ◽  
Oral Drug Delivery ◽  
Drug Product ◽  
Real Life ◽  
Drug Formulation ◽  
Oral Drug ◽  
Formulation Development ◽  
Drug Products

A thorough understanding of the behavior of drug formulations in the human gastrointestinal (GI) tract is essential when working in the field of oral drug development in a pharmaceutical company. For orally administered drug products, various GI processes, including disintegration of the drug formulation, drugrelease, dissolution, precipitation, degradation, dosage form transit and permeation, dictate absorption into the systemic circulation. These processes are not always fully captured in predictive in vitro and in silico tools, as commonly applied in the pre-clinical stage of formulation drug development. A collaborative initiative focused on the science of oral biopharmaceutics was established in 2012 between academic institutions and industrial companies to innovate, optimize and validate these in vitro and in silico biopharmaceutical tools. From that perspective, the predictive power of these models can be revised and, if necessary, optimized to improve the accuracy toward predictions of the in vivo performance of orally administered drug products in patients. The IMI/EFPIA-funded “Oral Bioavailability Tools (OrBiTo)” project aimed to improve our fundamental understanding of the GI absorption process. The gathered information was integrated into the development of new (or already existing) laboratory tests and computer-based methods in order to deliver more accurate predictions of drug product behavior in a real-life setting. These methods were validated with the use of industrial data. Crucially, the ultimate goal of the project was to set up a scientific framework (i.e., decision trees) to guide the use of these new tools in drug development. The project aimed to facilitate and accelerate the formulation development process and to significantly reduce the need for animal experiments in this area as well as for human clinical studies in the future. With respect to the positive outcome for patients, high-quality oral medicines will be developed where the required dose is well-calculated and consistently provides an optimal clinical effect. In a first step, this manuscript summarizes the setup of the project and how data were collected across the different work packages. In a second step, case studies of how this project contributed to improved knowledge of oral drug delivery which can be used to develop improved products for patients will be illustrated.

Formulation Development and Characterization of controlled release core in cup matrix tablets of venlafaxine HCl

2020 ◽  
Vol 15 ◽  
Author(s):  
Balaji Maddiboyina ◽  
Vikas Jhawat ◽  
Gandhi Sivaraman ◽  
Om Prakash Sunnapu ◽  
Ramya Krishna Nakkala ◽  
...  
Keyword(s):  
Controlled Release ◽  
Drug Release ◽  
Release Rate ◽  
Zero Order ◽  
Water Soluble ◽  
Matrix Tablets ◽  
Drug Dissolution ◽  
Crystalline Cellulose ◽  
Hydrophobic Polymers

Background: Venlafaxine HCl is a selective serotonin reuptake inhibitor which is given in the treatment of depression. The delivery of the drug at a controlled rate can be of great importance for prolonged effect. Objective: The objective was to prepare and optimize the controlled release core in cup matrix tablet of venlafaxine HCl using the combination of hydrophilic and hydrophobic polymers to prolong the effect with rate controlled drug release. Methods: The controlled release core in cup matrix tablets of venlafaxine HCl were prepared using HPMC K5, K4, K15, HCO, IPA, aerosol, magnesium sterate, hydrogenated castor oil and micro crystalline cellulose PVOK-900 using wet granulation technique. Total ten formulations with varying concentrations of polymers were prepared and evaluated for different physicochemical parameters such FTIR analysis for drug identification, In-vitro drug dissolution study was performed to evaluate the amount of drug release in 24 hrs, drug release kinetics study was performed to fit the data in zero order, first order, Hixson–crowell and Higuchi equation to determine the mechanism of drug release and stability studies for 3 months as observed. Results: The results of hardness, thickness, weight variation, friability and drug content study were in acceptable range for all formulations. Based on the In vitro dissolution profile, formulation F-9 was considered to be the optimized extending the release of 98.32% of drug up to 24 hrs. The data fitting study showed that the optimized formulation followed the zero order release rate kinetics and also compared with innovator product (flavix XR) showed better drug release profile. Conclusion: The core-in-cup technology has a potential to control the release rate of freely water soluble drugs for single administration per day by optimization with combined use of hydrophilic and hydrophobic polymers.

In vitro drug release testing of controlled release veterinary drug products

2000 ◽  
pp. 311-332 ◽  
Author(s):  
Michael J. Rathbone ◽  
Jingjian Shen ◽  
Colin R. Ogle ◽  
Shane Burggraaf ◽  
Craig R. Bunt
Keyword(s):  
Controlled Release ◽  
Drug Release ◽  
Veterinary Drug ◽  
In Vitro Drug Release ◽  
Drug Products ◽  
Release Testing

scholarly journals Formulation and in-vitro evaluation of ciprofloxacin HCL floating matrix tablets

2020 ◽  
Vol 2 (1) ◽  
pp. 01-06
Author(s):  
Dhulipalla Mounika ◽  
I. Deepika Reddy ◽  
K. Sai Chandralekha ◽  
Kapu Harika ◽  
Ramarao Nadendla ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Controlled Release ◽  
Drug Release ◽  
Matrix Tablets ◽  
Fickian Diffusion ◽  
In Vitro Dissolution ◽  
Oral Drug ◽  
Prolonged Release ◽  
Evaluation Parameters

Oral drug delivery is the most widely utilized route of administration among all the routes that have been explored for systemic delivery of drugs via pharmaceutical products of different dosage form. Oral route is considered most natural, uncomplicated, convenient and safe due to its ease of administration, patient acceptance and cost-effective manufacturing process. Gastroretentive drug delivery system was developed in pharmacy field and drug retention for a prolonged time has been achieved. The goal of this study was to formulate and in-vitro evaluate Ciprofloxacin HCl controlled release matrix floating tablets. Ciprofloxacin HCl floating matrix tablets were prepared by wet granulation method using two polymers such as HPMC K100M (hydrophilic polymer) and HPMC K15M. All the Evaluation parameters were within the acceptable limits. FTIR spectral analysis showed that there was no interaction between the drug and polymers. In-vitro dissolution study was carried out using USP dissolution test apparatus (paddle type) at 50 rpm. The test was carried out at 37 ± 0.5 0C in 900ml of the 0.1 N HCl buffer as the medium for eight hours. HPMC K100M shows a prolonged release when compared to HPMC K15M. These findings indicated that HPMC K100M can be used to develop novel gastroretentive controlled release drug delivery systems with the double advantage of controlled drug release at GIT pH. On comparing the major criteria in evaluation such as preformulation and in vitro drug release characteristics, the formulation F8 was selected as the best formulation, as it showed the drug content as 99±0.4% and swelling index ratio was 107.14, and in-vitro drug released 61.31±0.65% up to 8 hours. Results indicated that controlled Ciprofloxacin HCl release was directly proportional to the concentration of HPMC K100M and the release of drug followed non-Fickian diffusion. Based on all the above evaluation parameters it was concluded that the formulation batch F8 was found to be best formulation among the formulations F1 to F8 were prepared.

Small-scale in vitro methods for evaluating the impact of gastrointestinal transfer on luminal drug / drug product performance in the fasted state

2020 ◽  
Author(s):  
Πάτρικ Ο' Ντουάιρ
Keyword(s):  
Drug Product ◽  
Product Performance ◽  
Small Scale ◽  
In Vitro Methods ◽  
Drug Products ◽  
Fasted State ◽  
The Impact

Η βιοδιαθεσιμότητα ενός φαρμάκου μετά από per os χορήγηση επηρεάζεται από πολλές διαδικασίες. Η γαστρεντερική μεταφορά αποτελεί μια σημαντική φυσιολογική διαδικασία, που επηρεάζει της συγκεντρώσεις του φαρμάκου στο λεπτό έντερο, δηλαδή στην περιοχή από την οποία απορρόφουνται τις περισσότερες φορές τα per os χορηγούμενα φάρμακα. Στην παρούσα εργασία αναπτύχθηκαν δυο μικρής κλίμακας μέθοδοι για την εκτίμηση της σημασίας της γαστρεντερικής μεταφοράς στην απορρόφηση ενός φαρμάκου μετά από per os χορήγηση κατά τη διάρκεια της διαπεπτικής περιόδου. Οι μέθοδοι βασίστηκαν σε ένα διφασικό σύστημα διάλυσης δύο σταδίων και σε μια συσκευή διάλυσης-διαπέρασης δυο σταδίων. Η διφασική μέθοδος διάλυσης προσομοιώνει τη διαδικασία της μεταφοράς μέσω του εντερικού επιθηλίου με τη χρήση μιας στοιβάδας δεκανόλης. Η μέθοδος διάλυσης-διαπέρασης προσομοιώνει τη διαδικασία μεταφοράς μέσω του γαστρεντερικού επιθηλίου με τη χρήση μιας συνθετικής λιπιδικής μεμβράνης και ενός διαμερίσματος υποδοχής του φαρμάκου. Οι δυο μικρής κλίμακας μέθοδοι δυο σταδίων αναπτύχθηκαν και αξιολογήθηκαν με βάση δεδομένα δυο ασθενών βάσεων που ανήκουν στην Τάξη ΙΙ της Βιοφαρμακευτικής Ταξινόμησης των Φαρμάκων, της διπυριδαμόλης και της κετοκοναζόλης. Οι ρυθμοί καθίζησης, που υπολογίσθηκαν από τα δεδομένα των πειραμάτων με τις δυο μεθόδους, χρησιμοποιήθηκαν για την προσομοίωση των απεικονίσεων των συγκεντρώσεων στο πλάσμα μετά από χορήγηση σε ενήλικες με τη βοήθεια φυσιολογικών φαρμακοκινητικών μοντέλων. Οι τιμές των φαρμακοκινητικών παραμέτρων, που υπολογίσθηκαν από τις απεικονίσεις, συγκρίθηκαν με τις τιμές των φαρμακοκινητικών παραμέτρων, που είχαν υπολογισθεί από προηγούμενες κλινικές μελέτες των φαρμάκων σε υγιείς ενήλικες. Τα δεδομένα της διφασικής μεθόδου διάλυσης οδήγησαν σε καλύτερη εκτίμηση των φαρμακοκινητικών παραμέτρων των δυο ασθενών βάσεων. Τα δεδομένα της μεθόδου διάλυσης-διαπέρασης οδήγησαν σε υπερεκτίμηση της καθίζησης, πιθανότατα λόγω της αργής ροής μεταφοράς στο διαμέρισμα υποδοχής. Στη συνέχεια, οι δυο μικρής κλίμακας μέθοδοι δυο σταδίων αξιολογήθηκαν χρησιμοποιώντας φαρμακευτικά προϊόντα με αυξημένες δυνατότητες (enabling drug products) που περιλάμβαναν άμορφες στερεές διασπορές, ένα σύμπλοκο φαρμάκου με κυκλοδεξτρίνη και λιπιδικά προϊόντα. Για τη μελέτη των λιπιδικών προϊόντων η διφασική μέθοδος τροποποιήθηκε για να ενσωματωθεί και η διαδικασία της πέψης των εκδόχων. Συνολικά, η διφασική μέθοδος ήταν περισότερο χρήσιμη από τη μέθοδο-διάλυσης διαπέρασης και τα δεδομένα σχετίστηκαν καλύτερα με τα in vivo δεδομένα. Τέλος, η χρησιμότητα των δυο μικρής κλίμακας μεθόδων δυο σταδίων σε σχέση με δυο άλλες χρησιμοποιούμενες μεθόδους, τη διατάξη μικρού περιστρεφόμενου πτερυγίου Erweka και τη διάταξη ΒioGIT, μελετήθηκε με βάση δεδομένα δυο φαρμάκων που ανήκουν στην Τάξη ΙΙ της Βιοφαρμακευτικής Ταξινόμησης των Φαρμάκων, της δικλοφενάκης (ασθενές εξύ) και της ριτοναβίρης (ασθενής βάση). Με όλες τις μεθόδους, η δικλοφενάκη διαλύθηκε πολύ γρήγορα σε μέσα που προσομοιώνουν σε Επίπεδο ΙΙ τα περιεχόμενα του λεπτού εντέρου, τόσο μετά από μορφοποίηση σε σκόνη όσο και μετά από μορφοποίηση σε δισκίο. Φυσιολογική φαρμακοκινητική μοντελοποίηση των δεδομένων έδειξε, ότι μετά από χορήγηση προϊόντων άμεσης αποδέσμευσης δικλοφενάκης, η απορρόφηση εξαρτάται από τη γαστρική κένωση και τη μεταφορά μέσω του εντερικού επιθηλίου, ανεξάρτητα από τον τύπο του προϊόντος. Αντίθετα, η άμορφη στερεή διασπορά της ριτοναβίρης οδηγεί σε καθίζηση του φαρμάκου στον αυλό του λεπτού εντέρου. Όλες οι μέθοδοι που προσομοίωσαν την αλλαγή των συνθηκών από το στόμαχο στο λεπτό έντερο προσομοίωσαν επαρκώς την επίδραση του μειωμένου ρυθμού έκκρισης γαστρικού οξέος στη συμπεριφορά του προϊόντος in vivo. Με βάση τα δεδομένα συνολικά, κάθε μέθοδος παρουσιάζει ιδιαίτερα προτερήματα και αδυναμίες. Συνολικά, με βάση τα αποτελέσματα της παρούσας μελέτης η διφασική μέθοδος θα μπορούσε να διευκολύνει σημαντικά στα αρχικά στάδια της ανάπτυξης νέων φαρμάκων, ιδιαίτερα αν συνδυαστεί με φυσιολογικά φαρμακοκινητικά μοντέλα.

scholarly journals Evaluation of Excipient Risk in BCS Class I and III Biowaivers

2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Melissa Metry ◽  
James E. Polli
Keyword(s):  
Drug Product ◽  
Scale Up ◽  
Drug Formulation ◽  
Product Regulatory ◽  
Drug Bioavailability ◽  
Drug Products ◽  
Fda Guidance ◽  
Regulatory Guidance

AbstractThe objective of this review article is to summarize literature data pertinent to potential excipient effects on intestinal drug permeability and transit. Despite the use of excipients in drug products for decades, considerable research efforts have been directed towards evaluating their potential effects on drug bioavailability. Potential excipient concerns stem from drug formulation changes (e.g., scale-up and post-approval changes, development of a new generic product). Regulatory agencies have established in vivo bioequivalence standards and, as a result, may waive the in vivo requirement, known as a biowaiver, for some oral products. Biowaiver acceptance criteria are based on the in vitro characterization of the drug substance and drug product using the Biopharmaceutics Classification System (BCS). Various regulatory guidance documents have been issued regarding BCS-based biowaivers, such that the current FDA guidance is more restrictive than prior guidance, specifically about excipient risk. In particular, sugar alcohols have been identified as potential absorption-modifying excipients. These biowaivers and excipient risks are discussed here.

scholarly journals Formulation and Evaluation of Novel Formulation for Diabetes Induced Hypertension using Modified Innate Superdisintegrant

2020 ◽  
Vol 10 (5) ◽  
pp. 240-250
Author(s):  
Vinay Pandit ◽  
Dipanker Kashive ◽  
Tarun Kumar Sharma
Keyword(s):  
The Body ◽  
Drug Dissolution ◽  
In Vitro Dissolution ◽  
Direct Compression ◽  
Compression Technique ◽  
Disintegration Time ◽  
Opuntia Ficus Indica ◽  
Cardiovascular Morbidity And Mortality ◽  
Induced Hypertension

Objectives: Diabetes is a chronic disease and is a group of metabolic disorders characterized by high levels of sugar in blood (hyperglycemia). Hypertension is a major modifiable risk factor for cardiovascular morbidity and mortality in patients with diabetes. The objective of this research is to formulate Fast dissolving tablets of Pioglitazone and Cilnidipine for the effective treatment of diabetes induced hypertension. Methods: Six formulations were prepared by direct compression technique by using Opuntia ficus-indica as an innate superdisintegrant. Result and Discussion: All the formulations were subjected for precomprression, post compression parameters and shows all the data within the specific limits. F5 formulation with the mixture of polymers viz. Opuntia ficus indica, SSG, croscarmellose sodium, magnesium stearate, DiCOM showed comparatively fast disintegration and best release of drug than that of all other formulation. The tablets of F5 formulation disintegrated within 18.53 seconds can provide fast relief in the body. The in-vitro dissolution results revealed that the drug release of F5 formulation tablets was more than 90% for Pioglitazone and near to 70% for Cilnidipine within 30 minutes. Stability studies were performed on F5 formulation tablets showed no significant changes in color, disintegration time and in-vitro dissolution which showed that appearance of tablets was having no effect. Conclusion: Fast dissolving tablets of Pioglitazone and Cilnidipine can be successfully prepared using direct compression technique and it will enhance the drug dissolution, which will further increase absorption and bioavailability of both drugs. Keywords: Pioglitazone, Cilnidipine, diabetes induced hypertension, fast dissolving tablets, direct compression.

scholarly journals Studies on Bio-adhesion of Matrix Tablets: I. Release Profile of Theophylline Anhydrous

1970 ◽  
Vol 5 (1) ◽  
pp. 33-37
Author(s):  
Md. Shamsuddin ◽  
Parvin Akter ◽  
Md. Ziaur Rahman Khan ◽  
Jakir Ahmed Chowdhury ◽  
Md. Selim Reza
Keyword(s):  
Controlled Release ◽  
Mucous Membrane ◽  
Xanthan Gum ◽  
In Vitro Release ◽  
Gastric Fluid ◽  
Release Profile ◽  
Matrix Tablets ◽  
Drug Dissolution ◽  
Burst Release

Controlled release matrix tablets of theophylline anhydrous were designed with different types of bioadhesive polymers. HPMC 15 cps and 50 cps, Na-CMC, Gelatin, Xanthun gum and PVP K-30 were selected to formulate matrix tablets. Tablets of theophylline were prepared by direct compression method and were subjected to in vitro drug dissolution for 8 hrs in a gastric fluid media by using thermal shaker with a shaking speed of 50 rpm at a temperature of 37 ± 0.5°C. The in vitro release study as well as retention time of bioadhesive tablets on mucous membrane were investigated to develop a bioadhesive polymer based controlled release delivery system and to evaluate the performance of such delivery device. Na-CMC, HPMC and Xanthan gum based tablets showed greater bio-adhesive strength where as gelatin and PVP K-30 based tablets showed poor bioadhesive strength. Na-CMC and Xanthun gum loaded tablets were not discharged from the mucous membrane and these tablets were fully dissolved in the gastric fluid. Xanthan gum, Na-CMC and HPMC based formulation showed nearly zero-order release. On the contrary, gelatin and PVP K-30 based formulation showed a burst release within one hour of dissolution. Key words: Bio-adhesion, Release profile, theophylline anhydrous. Dhaka Univ. J. Pharm. Sci. Vol.5(1-2) 2006 The full text is of this article is available at the Dhaka Univ. J. Pharm. Sci. website

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