scholarly journals In Vivo Predictive Dissolution Testing of Montelukast Sodium Formulations Administered with Drinks and Soft Foods to Infants

2020 ◽  
Vol 21 (7) ◽  
Author(s):  
J. Martir ◽  
T. Flanagan ◽  
J. Mann ◽  
N. Fotaki
Keyword(s):  
Drug Product ◽  
Drug Dissolution ◽  
Simulated Gastric Fluid ◽  
Dissolution Testing ◽  
Fed State ◽  
Fasted State ◽  
Direct Administration ◽  
The Impact

Abstract In vitro dissolution testing conditions that reflect and predict in vivo drug product performance are advantageous, especially for the development of paediatric medicines, as clinical testing in this population is hindered by ethical and technical considerations. The aim of this study was to develop an in vivo predictive dissolution test in order to investigate the impact of medicine co-administration with soft food and drinks on the dissolution performance of a poorly soluble compound. Relevant in vitro dissolution conditions simulating the in vivo gastrointestinal environment of infants were used to establish in vitro-in vivo relationships with corresponding in vivo data. Dissolution studies of montelukast formulations were conducted with mini-paddle apparatus on a two-stage approach: infant fasted-state simulated gastric fluid (Pi-FaSSGF; for 1 h) followed by either infant fasted-state or infant fed-state simulated intestinal fluid (FaSSIF-V2 or Pi-FeSSIF, respectively; for 3 h). The dosing scenarios tested reflected in vivo paediatric administration practices: (i.) direct administration of formulation; (ii.) formulation co-administered with vehicles (formula, milk or applesauce). Drug dissolution was significantly affected by co-administration of the formulation with vehicles compared with after direct administration of the formulation. Montelukast dissolution from the granules was significantly higher under fed-state simulated intestinal conditions in comparison with the fasted state and was predictive of the in vivo performance when the granules are co-administered with milk. This study supports the potential utility of the in vitro biorelevant dissolution approach proposed to predict in vivo formulation performance after co-administration with vehicles, in the paediatric population.

scholarly journals Impact of Food and Drink Administration Vehicles on Paediatric Formulation Performance Part 2: Dissolution of Montelukast Sodium and Mesalazine Formulations

2020 ◽  
Vol 21 (7) ◽  
Author(s):  
J. Martir ◽  
T. Flanagan ◽  
J. Mann ◽  
Nikoletta Fotaki
Keyword(s):  
Drug Formulation ◽  
Drug Dissolution ◽  
Simulated Gastric Fluid ◽  
Dissolution Testing ◽  
Drug Bioavailability ◽  
Age Appropriate ◽  
Direct Administration ◽  
The Impact ◽  
Paediatric Formulation

Abstract Paediatric medicines are not always age-appropriate, causing problems with dosing, acceptability and adherence. The use of food and drinks as vehicles for medicine co-administration is common practice, yet the impact on drug bioavailability, safety and efficacy remains unaddressed. The aim of this study was to use in vitro dissolution testing, under infant simulating conditions, to evaluate the effect of co-administration with vehicles on the dissolution performance of two poorly soluble paediatric drugs. Dissolution studies of mesalazine and montelukast formulations were conducted with mini-paddle apparatus on a two-stage approach: simulated gastric fluid followed by addition of simulated intestinal fluid. The testing scenarios were designed to reflect daily administration practices: direct administration of formulation; formulation co-administered with food and drinks, both immediately after mixing and 4 h after mixing. Drug dissolution was significantly affected by medicine co-administration with vehicles, compared to the direct administration of formulation. Furthermore, differences were observed on drug dissolution when the formulations were mixed with different vehicles of the same subtype. The time between preparation and testing of the drug-vehicle mixture also impacted dissolution behaviour. Drug dissolution was shown to be significantly affected by the physicochemical properties and composition of the vehicles, drug solubility in each vehicle and drug/formulation characteristics. Ultimately, in this study, we show the potential of age-appropriate in vitro dissolution testing as a useful biopharmaceutical tool for estimating drug dissolution in conditions relevant to the paediatric population. The setup developed has potential to evaluate the impact of medicine co-administration with vehicles on paediatric formulation performance.

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 Comparative survival of commercial probiotic formulations: tests in biorelevant gastric fluids and real-time measurements using microcalorimetry

2015 ◽  
Vol 6 (1) ◽  
pp. 141-151 ◽  
Author(s):  
M. Fredua-Agyeman ◽  
S. Gaisford
Keyword(s):  
Real Time ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Fed State ◽  
Fasted State ◽  
Nutritional Advice ◽  
Freeze Dried ◽  
Viable Bacteria

The large number of probiotic products now available makes the decision about which product to choose difficult both for the consumer and for the specialist providing dietary/nutritional advice. Data on the viability of the bacteria in these products, in an in vivo situation, are therefore important. This study was designed to explore the comparative health and survival of probiotic species in various commercial formulations, using more realistic test systems. This might allow further understanding of factors that must be controlled to optimise the delivery of live healthy bacteria to the lower gut. A total of eight commercially available probiotic preparations were selected for enumeration tests and in vitro gastric tolerance tests. Tolerance assays were conducted in porcine gastric fluid (PGF) fed and fasted state (pH 3.4±0.04), simulated gastric fluid (SGF, pH adjusted to 1.2 and 3.4) and fasted state simulated gastric fluid (FaSSGF, pH adjusted to 1.6 and 3.4). Isothermal microcalorimetry was also used to measure real-time growth of probiotics after exposure to simulated gastric fluid. Results from the enumeration tests indicated that recovery of viable organisms per dose is the same as or better than the stated label claims for liquid-based formulations, but lower than the stated claim for freeze-dried products. Results from the in vitro tolerance tests overall suggest that the PGF provided a harsher environment than the simulated systems at similar pH. In general, liquid-based products tested tended to give superior results in terms of survival compared with the freeze-dried products tested. Results from tests in the fed state in PGF suggested that food greatly affects viability. Microcalorimetric data showed that for some products probiotic species were able to grow following exposure to gastric fluid, suggesting that viable bacteria reach the gut in vivo.

scholarly journals Crushed Tablets: Does the Administration of Food Vehicles and Thickened Fluids to Aid Medication Swallowing Alter Drug Release?

2014 ◽  
Vol 17 (2) ◽  
pp. 207 ◽  
Author(s):  
Yady Juliana Manrique-Torres ◽  
Danielle J Lee ◽  
Faiza Islam ◽  
Lisa M Nissen ◽  
Julie A.Y. Cichero ◽  
...  
Keyword(s):  
Drug Release ◽  
Orange Juice ◽  
Immediate Release ◽  
Drug Dissolution ◽  
In Vitro Dissolution ◽  
Simulated Gastric Fluid ◽  
Drug Bioavailability ◽  
Thickening Agents

Purpose. To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Methods. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Results. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Conclusions. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Effects of Hydrophilic Carriers on Structural Transitions and In Vitro Properties of Solid Self-Microemulsifying Drug Delivery Systems

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 267 ◽  
Author(s):  
Tao Yi ◽  
Jifen Zhang
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Commercial Application ◽  
Simulated Gastric Fluid ◽  
Structural Transitions

Self-microemulsifying drug delivery systems (SMEDDS) offer potential for improving the oral bioavailability of poorly water-soluble drugs. However, their susceptibilities during long term storage and in vivo precipitation issues limit their successful commercial application. To overcome these limitations, SMEDDS can be solidified with solid carriers, thus producing solid self-microemulsifying drug delivery systems (S-SMEDDS). In this study, effects of various hydrophilic carriers on structural transitions and in vitro properties of S-SMEDDS were investigated in order to set up in vitro methods for screening out appropriate carriers for S-SMEDDS. Liquid SMEDDS was prepared and characterized using nimodipine as a model drug. The effects of various hydrophilic carriers on internal microstructure and solubilization of SMEDDS were investigated by conductivity measurement and in vitro dispersion test. The results showed that hydrophilic carriers including dextran 40, maltodextrin and PVP K30 seemed to delay the percolation transition of SMEDDS, allowing it to maintain a microstructure that was more conducive to drug dissolution, thus significantly increasing the solubilization of nimodipine in the self-microemulsifying system and decreasing drug precipitation when dispersed in simulated gastric fluid. S-SMEDDS of nimodipine were prepared by using spray drying with hydrophilic carriers. The effects of various hydrophilic carriers on in vitro properties of S-SMEDDS were investigated by using SEM, DSC, PXRD and in vitro dissolution. The results showed that properties of hydrophilic carriers, especially relative molecular mass of carriers, had obvious influences on surface morphologies of S-SMEDDS, reconstitution of microemulsion and physical state of nimodipine in S-SMEDDS. Considering that in vitro properties of S-SMEDDS are closely related to their pharmacokinetic properties in vivo, the simple and economical in vitro evaluation methods established in this paper can be used to screen solid carriers of S-SMEDDS well.

scholarly journals Gastrin and Nitric Oxide Production in Cultured Gastric Antral Mucosa Are Altered in Response to a Gastric Digest of a Dietary Supplement

2021 ◽  
Vol 8 ◽  
Author(s):  
Jennifer L. MacNicol ◽  
Wendy Pearson
Keyword(s):  
Nitric Oxide ◽  
Cell Viability ◽  
Dietary Supplement ◽  
Culture Media ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Antral Mucosa ◽  
The Impact

In vitro organ culture can provide insight into isolated mucosal responses to particular environmental stimuli. The objective of the present study was to investigate the impact of a prolonged culturing time as well as the addition of acidic gastric fluid into the in vitro environment of cultured gastric antral tissue to evaluate how altering the commonly used neutral environment impacted tissue. Furthermore, we aimed to investigate the impact of G's Formula, a dietary supplement for horses, on the secretion of gastrin, interleukin1-beta (IL-1β), and nitric oxide (NO). These biomarkers are of interest due to their effects on gastric motility and mucosal activity. Gastric mucosal tissue explants from porcine stomachs were cultured in the presence of a simulated gastric fluid (BL, n = 14), simulated gastric fluid containing the dietary supplement G's Formula (DF, n = 12), or an equal volume of phosphate buffered saline (CO, n = 14). At 48 and 60 h, 10−5 M carbachol was used to stimulate gastrin secretion. Cell viability was assessed at 72 h using calcein and ethidium-homodimer 1 staining. Media was analyzed for gastrin, IL-1β, and NO at 48, 60, and 72 h. There were no effects of treatment or carbachol stimulation on explant cell viability. Carbachol resulted in a significant increase in gastrin concentration in CO and DF treatments, but not in BL. NO was higher in CO than in BL, and NO increased in the CO and DF treatments but not in BL. In conclusion, the addition of carbachol and gastric digests to culture media did not impact cell viability. The use of an acidic gastric digest (BL) reduced the effect of cholinergic stimulation with carbachol at a concentration of 10−5 M and reduced NO secretion. The addition of the dietary supplement to the gastric digest (DF) appeared to mediate these effects within this model. Further research is required to evaluate the specific effects of this dietary supplement on direct markers of mucosal activity and the functional relevance of these results in vivo.

scholarly journals 1115. Evaluation of Gepotidacin (GSK2140944) Pharmacokinetics and Food Effect in Japanese Subjects

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S650-S651
Author(s):  
Mohammad Hossain ◽  
Courtney Tiffany ◽  
Aline Barth ◽  
Aparna Raychaudhuri ◽  
Etienne F Dumont
Keyword(s):  
Tolerability Profile ◽  
Time Curve ◽  
Fed State ◽  
Fasted State ◽  
Drug Concentrations ◽  
Tract Infections ◽  
Oral Doses ◽  
Japanese Subjects

Abstract Background Gepotidacin, a novel, first-in-class triazaacenaphthylene antibiotic, inhibits bacterial replication and has in vitro and in vivo activity against key pathogens, including drug-resistant strains, associated with a range of infections. Gepotidacin is currently in Phase 3 clinical studies for the treatment of uncomplicated urinary tract infections and gonorrhea. This study (NCT02853435) was designed to assess gepotidacin pharmacokinetics (PK) in Japanese subjects (fasted and fed). Methods A tablet formulation of 750 mg gepotidacin free base was used in the study, which was conducted in two parts: Part 1, gepotidacin PK was assessed following 1500 and 3000 mg single oral doses in the fasted state; and Part 2, gepotidacin PK was assessed following 1500, 2250, and 3000 mg single oral doses in the fed state. Serial blood and urine samples were collected in both study parts. Results Part 1: The area under the plasma drug concentration-time curve from time 0 to infinity (AUC[0–∞]) and maximum observed concentration (Cmax) were slightly higher in Japanese subjects than in Caucasian subjects at the same dose levels and with the same formulation. Following gepotidacin dosing in the fasted state, the 1500 mg dose was tolerated, while the 3000 mg dose was poorly tolerated with mild or moderate gastro-intestinal adverse effects (GI AEs) reported by most subjects shortly after being dosed. Part 2: PK was linear with doses in the range of 1500–3000 mg. Administration of gepotidacin 3000 mg tablets in the fed state slightly reduced Cmax and slightly increased AUC at the 3000 mg dose level. The 1500 and 2250 mg doses were tolerated while the 3000 mg dose was better tolerated compared to the fasted state with fewer and short-lived GI AEs, mostly mild in intensity. After oral administration of 1500–3000 mg, high urine drug concentrations were achieved, remaining above the minimum inhibitory concentration of 4 μg/mL for up to 24 hours. Conclusion The PK of gepotidacin following administration of a single oral dose to Japanese subjects was linear from 1500–3000 mg and food decreased Cmax without impact on exposure (AUC). Administration of gepotidacin with food resulted in an improved GI tolerability profile at the higher dose tested in Japanese subjects. Disclosures Mohammad Hossain, PhD, GlaxoSmithKline plc. (Employee, Shareholder, Former employee of and past/current shareholder in GlaxoSmithKline plc.) Courtney Tiffany, BSc, GlaxoSmithKline plc. (Employee, Shareholder, Former employee of and past/current shareholder in GlaxoSmithKline plc.) Aline Barth, MSC;PHD, GlaxoSmithKline plc. (Employee, Shareholder, Employee of and shareholder in GlaxoSmithKline plc.) Aparna Raychaudhuri, Ph.D., GlaxoSmithKline plc. (Employee, Shareholder, Former employee of and past/current shareholder in GlaxoSmithKline plc.) Etienne F. Dumont, MD, GlaxoSmithKline plc. (Employee, Shareholder, Former employee of and shareholder in GlaxoSmithKline plc.)

scholarly journals IN VITRO CEFIXIME DISSOLUTION IN PHARMACOPEIA-RECOMMENDED MEDIUM AND SIMULATED GASTROINTESTINAL FLUIDS: A COMPARATIVE STUDY

2019 ◽  
pp. 158-160
Author(s):  
ANES AM THABIT ◽  
AHMED MS AL-GHANI
Keyword(s):  
The United States ◽  
Drug Dissolution ◽  
In Vitro Dissolution ◽  
Simulated Intestinal Fluid ◽  
Fed State ◽  
The Difference ◽  
The One ◽  
States Pharmacopeia

Objectives: The aim of this study was to compare in vitro dissolution of cefixime in a pharmacopeial-recommended medium and in simulated gastrointestinal fluids. Methods: Before dissolution testing, the drug content in the tested materials was determined by ultraviolet spectrophotometer. The dissolution media used in this study were recommended by the United States Pharmacopeia (USP) as well as four different media that mimic gastric and intestinal fluids in fed and fasted states. The tested materials included the pure drug and two 0.2-g capsule brands (original and test). Results: The pharmacopeial medium showed no difference in both extent and rate of the drug dissolution between the tested materials. In the contrary, the difference was significant when the simulated fluids were used. Moreover, it was found that the simulated intestinal fluid (SIF) of fed state showed 21–32% decrement in the drug dissolution compared to that of the corresponding fasted-state simulated fluid. Indeed, this finding agreed those of in vivo bioavailability studies published in literature. Conclusion: The SIF is much more valid as a medium for in vitro testing of cefixime capsule than the one recommended by the USP.

scholarly journals Deciphering nifedipine in vivo delivery from modified release dosage forms: Identification of food effect

2015 ◽  
Vol 65 (4) ◽  
pp. 427-441 ◽  
Author(s):  
Marija Ilić ◽  
Ivan Kovačević ◽  
Jelena Parojčić
Keyword(s):  
In Silico ◽  
Food Effect ◽  
Drug Product ◽  
Dosage Forms ◽  
In Vitro Dissolution ◽  
Dissolution Testing ◽  
Modified Release ◽  
In Vivo Delivery

Abstract With the increased reliance on in vitro dissolution testing as an indicator of in vivo drug behavior and the trend towards the in silico modeling of dosage form performance, the need for bioperformance dissolution methodology development has been enhanced. Determination of the in vivo drug delivery profile is essential for the bioperformance dissolution test development and in vitro/in vivo correlation modeling, as well as the understanding of absorption mechanisms. The aim of this study was to compare different methods in terms of their usefulness and applicability in deciphering in vivo delivery of nifedipine administered in modified release dosage forms. A detailed survey of publications on nifedipine pharmacokinetics was done and used to identify the magnitude of food effect. In vitro dissolution testing was performed under various experimental conditions. Obtained results indicate the potential for using the developed in silico model coupled with discriminative in vitro dissolution data for identification of the in vivo drug product behavior

scholarly journals Biorelevant dissolution models to assess precipitation of weak base drug

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 2165-2172
Author(s):  
Viviane Annisa ◽  
Teuku Nanda Saifullah Sulaiman ◽  
Agung Endro Nugroho
Keyword(s):  
Small Intestine ◽  
Gastric Fluid ◽  
Water Soluble ◽  
Simulated Gastric Fluid ◽  
Intestinal Fluid ◽  
Weak Base ◽  
Fluid Medium ◽  
Fed State ◽  
Fasted State ◽  
The Impact

The impact of precipitation can affect the amount of drug absorbed, thereby affecting the amount of drug in the systemic body. The precipitation process is preceded by a supersaturation phase, caused by decreased drug solubility in the gastrointestinal tract. This precipitation occurs for weak base drugs with low solubility. When the drug entering the small intestine, the solubility of weak base drugs decrease, then occurs supersaturation, which leads to precipitation, so that drug precipitation is one of a challenge for the pharmaceutical industry in drug development. Precipitation testing of water-soluble weak base drugs can be carried out by the pH shift method to describe the gastrointestinal pH gradient from gastric to small intestine. This pH change can cause supersaturation and then trigger precipitation, especially for weak base drugs. The methods that can used to assess precipitation drug is modification of the USP dissolution which are two compartment and multi compartment model. The choice of dissolution medium play an important role in the test results. The use of bio relevant medium can produce closer in vitro and in vivo correlations than the use of buffers. Generally, the medium used to simulate the weakly condition in the small intestine is FaSSIF (Fasted State Simulated Intestinal Fluid) or FeSSIF (Fed State Stimulate Intestinal Fluid) medium. The medium used to simulate the acidic condition in the stomach is FaSSGF (Fasted state simulated gastric fluid) or FeSSGF (Fed state simulated gastric fluid) medium.

Sign in / Sign up

Export Citation Format

Share Document