Predicting pharmacokinetic parameters by convolution: An in vitro approach for investigating bifunctional capsulated dosage form

2020 ◽  
Vol 60 ◽  
pp. 102078
Author(s):  
Amit Porwal ◽  
Harinath Dwivedi ◽  
Kamla Pathak
Keyword(s):  
Dosage Form ◽  
Pharmacokinetic Parameters

scholarly journals Comparative analysis of pharmacokinetic parameters of transdermal and intramuscular administration of Galavit®

2021 ◽  
Vol 23 (2) ◽  
pp. 114-121
Author(s):  
E. G. Kuznetsova ◽  
O. M. Kuryleva ◽  
L. A. Salomatina ◽  
S. V. Kursakov ◽  
Z. Z. Gonikova ◽  
...  
Keyword(s):  
Dosage Form ◽  
Animal Experiments ◽  
The Body ◽  
Intramuscular Administration ◽  
Pharmacokinetic Parameters ◽  
Therapeutic System ◽  
Transdermal Administration ◽  
Maximum Serum ◽  
Transdermal Therapeutic System

Introduction. Immunomodulator Galavit® is a promising domestic drug for the prevention and treatment of various infectious diseases. Earlier, the authors have developed and investigated in vitro its new dosage form – transdermal therapeutic system (TTS). Positive results from experiments made it possible to proceed to the study of the pharmacokinetic parameters of Galavit® TTS in animals.Objective: to compare the pharmacokinetic parameters of intramuscular and transdermal administration of immunomodulator Galavit® in animal experiments.Materials and methods. Sodium aminodihydrophthalazinedione was used as a substance in the form of a powder to prepare a solution for intramuscular administration of 100 mg (trade name Galavit®, manufacturer SELVIM LLC). The pharmacokinetics of transdermal and intramuscular injections were studied in male Chinchilla rabbits weighing 4.5–5.0 kg. Serum sodium aminodihydrophthalazinedione concentrations in animals were determined by highperformance liquid chromatography using a specially developed technique.Results. In contrast to the injection method, a prolonged and uniform inflow of the drug substance (MP) into the body is observed for percutaneous administration of sodium aminodihydrophthalazinedione. The maximum serum Galavit® concentration for a 40 mg dose (0.172 ± 0.054 μg/mL) and for a 80 mg dose (1.16 ± 0.22 μg/mL) remained at a constant level for 9 and 8 hours, respectively. The relative bioavailability of the Galavit® transdermal therapeutic system was 0.65 and 1.06 for the same doses.Conclusion. Application of Galavit® 80 mg transdermal therapeutic system provides bioavailability that is similar to the intramuscular administration of this drug at the same dose. At the same time, its maximum serum concentration significantly decreases and the retention time of Galavit® in the body increases by more than 10 times, which can contribute to prolongation of the drug effect. Due to the current growing interest in the use of immunomodulator Galavit® for coronavirus infection COVID-19, the development and study of a new dosage form is a promising task

Erythrocytes as Carriers of Indinavir: Preparation, Characterization, In vitro and In vivo Pharmacokinetic Evaluation in Rats

2017 ◽  
Vol 10 (1) ◽  
pp. 3573-3581
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Shiva Krishna A ◽  
Ramesh M ◽  
Suresh G ◽  
Jyothi Sri S
Keyword(s):  
Sustained Release ◽  
Dosage Form ◽  
Antiretroviral Drugs ◽  
Pharmacokinetic Parameters ◽  
Intravenous Route ◽  
Rat Erythrocytes ◽  
Human Immuno Deficiency Virus ◽  
Equal Dose

Indinavir is a protease inhibitor of the human immuno-deficiency virus. Indinavir is commercially available as capsule of 200 mg and 400 mg. Adult dose is 800 mg every 8 h. i.e., 2400 mg per day is equivalent to 6 capsules per day. No other dosage form is available in the market. Sustained release dosage form of indinavir can produce maximum therapeutic effect with minimum side effects and achieve better patient compliance. Various carriers have  been used for the drug targeting among which cellular carriers such as erythrocytes offer greater potential advantages than other system.  The drug is never free in circulation thus reducing toxicity and the drug half-life in circulation increases thus kinetic patterns. Antiretroviral-loaded erythrocytes offer a promising therapy against HIV owing to their potential to deliver this kind of drugs to macrophages and reticulo-endothelial (RES) tissues. The aim of the present investigation was to develop and optimize antiretroviral indinavir encapsulated in rat erythrocytes. In this study, the encapsulation of indinavir by rat erythrocytes prepared and compared with indinavir dissolved in normal saline. The prepared formulations were administered to rats by intravenous route and plasma samples was analysed by LC-MS/MS technique. The pharmacokinetic parameters were calculated using Win-nonlin software. The prepared indinavir loaded erythrocytes showed enhanced bioavailability in equal dose due to higher extent of absorption owing to its retention in erythrocytes and releasing the drug slowly. Indinavir demonstrated a sustained release from loaded erythrocytes over a period of 36 h, which suggests a potential use of the erythrocyte as a slow systemic release system for antiretroviral drugs.

scholarly journals Effect of physicochemical properties on the pharmacokinetic parameters of the new representative of benzothiazinones antituberculosis drug macozinonе

2020 ◽  
Vol 92 (12) ◽  
pp. 165-171
Author(s):  
A. L. Khokhlov ◽  
A. O. Mariandyshev ◽  
V. S. Shcherbakova ◽  
I. V. Ozerova ◽  
Yu. G. Kazaishvili ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Dosage Form ◽  
Empty Stomach ◽  
Acetate Buffer Solution ◽  
Reverse Direction ◽  
Pharmacokinetic Parameters ◽  
Biorelevant Media ◽  
Treatment Regimens

Introduction.Tuberculosis (TB) is one of the top ten causes of death worldwide. Improvement of the treatment options via development of new drugs and treatment regimens that would be more convenient for patients is one of key options of improving the effecacy of the TB prevention and careis. Since the creation of new treatment regimens by minimizing the number of the drugs used and reducing the duration of treatment is the most promising and correct direction, macozinone, a new candidate of the benzothiazinone series, can become the basis for development of new chemotherapy regimens for drug-resistant forms of TB including the combination of macozinone with the most effective modern anti-TB drugs. Aim.Comparative evaluation of the pharmacokinetic properties of macozinone capsules 80 mg and the new dosage form a dispersible tablet for preparation of oral solution. Materials and methods.Solubility of the substance macozinone in biorelevant media in vitro, permeability of macozinone in the test Caco-2 in vitro, as well as pharmacokinetics of macozinone in dogs in vivo were evaluated. Results.The solubility assessment in biorelevant media showed that the average limit of macozinone substance dissolution in the pH 5.0 acetate buffer solution was from 6 to 9 mg/l, in FaSSIF medium (fasted) from 2.5 to 4 mg/l, and in FeSSIF medium (after meals) from 16.8 to 29 mg/l. It is established that the cell permeability of the pharmaceutical substance macozinone in the CACO-2 test system is on average 2.510-6cm/s in the forward direction from the apical to basolateral cell membrane, and 1.510-6cm/s in the reverse direction, which corresponds to low permeability. The main pharmacokinetic parameters of macozinone dispersable tablets 160 mg, after dosing with food and on an empty stomach, as well as capsules 80 mg, when administered on an empty stomach in vivo studies in dogs are presented. Discussion.The specific physicochemical properties of macozinone, the problems of developing the new dosage form, as well as ways of solving some of them are presented. Conclusion.In the process of new dosage forms development, the existing chemical properties of the macozinone substance should be considered. One of the promising ways of increasing bioavailability and, consiquently, efficacy is development a fundamentally new drug form with modified release within the absorption window.

scholarly journals Pharmacoscintigraphic evaluation and antidiabetic efficacy of gliclazide-loaded 99mTc-labelled mucoadhesive microspheres

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ripunjoy Bordoloi ◽  
Abdul Baquee Ahmed ◽  
Kunal Bhattacharya
Keyword(s):  
Dosage Form ◽  
Gamma Scintigraphy ◽  
Pharmacokinetic Parameters ◽  
Scanning Electron Micrographs ◽  
Drug Bioavailability ◽  
Duration Of Action ◽  
Study Objective ◽  
Release Study ◽  
Gastro Retentive

Abstract Background The current study was carried out to evaluate the possible application of Musa balbisiana starch in formulation of mucoadhesive microsphere for oral delivery of gliclazide (GLZ). The study objective was to improve the oral bioavailability along with prolongation of its duration of action for a better glycaemic control. Ionic gelation technique was employed in formulating the dosage form. Optimization of the batches was carried out by response surface methodology using 32 full factorial designs. The microsphere prepared was characterized for several parameters along with its in vitro release study. The gastrointestinal transit of the optimized batch of prepared microspheres after oral administration was studied in rabbits by using the gamma scintigraphy technique utilizing 99mTc as the labelling agent in the presence of stannous chloride. Also, the optimized batch was studied for its pharmacokinetic parameters. Moreover, the antidiabetic efficacy of the prepared microsphere was evaluated in rats by using the streptozotocin (STZ)-induced diabetic model. Results The factorial design experiment resulted in an optimum formulation coded as F8. The compatible nature of the drug and excipient was revealed from FTIR, DSC and IST studies. The scanning electron micrographs also showed the occurrence of spherical microspheres having a smooth surface. The in vitro release study provided an evidence of an initial burst effect that was followed by a prolong release phase. The pharmacokinetic parameters justified the ability of the prepared dosage form in sustaining the drug release with a 2.7-fold enhancement in drug bioavailability. The images obtained during the gamma scintigraphy study suggested the gastro-retentive nature of the dosage form with the gastro-retentive ability for more than 4 h. Also, the pharmacodynamics study carried out in diabetic rat model confirmed about the better efficacy of the dosage form in lowering the elevated blood glucose level. Conclusion The overall study data provide valuable information about the potential of this banana starch in formulation of a mucoadhesive dosage form that can be used for enhancement of bioavailability of drug-like gliclazide which in turn can provide a beneficial effect in the management of diabetes.

Significance of In-Vitro and In-Vivo Correlation in Drug Delivery System

2018 ◽  
Vol 4 (4) ◽  
pp. 523-531
Author(s):  
Hina Mumtaz ◽  
Muhammad Asim Farooq ◽  
Zainab Batool ◽  
Anam Ahsan ◽  
Ashikujaman Syed
Keyword(s):  
Dosage Form ◽  
Pharmaceutical Preparations ◽  
Pharmacokinetic Profile ◽  
In Vitro Dissolution ◽  
Time Saving ◽  
Pharmaceutical Dosage Form ◽  
Short Period ◽  
Form Development

The main purpose of development pharmaceutical dosage form is to find out the in vivo and in vitro behavior of dosage form. This challenge is overcome by implementation of in-vivo and in-vitro correlation. Application of this technique is economical and time saving in dosage form development. It shortens the period of development dosage form as well as improves product quality. IVIVC reduce the experimental study on human because IVIVC involves the in vivo relevant media utilization in vitro specifications. The key goal of IVIVC is to serve as alternate for in vivo bioavailability studies and serve as justification for bio waivers. IVIVC follows the specifications and relevant quality control parameters that lead to improvement in pharmaceutical dosage form development in short period of time. Recently in-vivo in-vitro correlation (IVIVC) has found application to predict the pharmacokinetic behaviour of pharmaceutical preparations. It has emerged as a reliable tool to find the mode of absorption of several dosage forms. It is used to correlate the in-vitro dissolution with in vivo pharmacokinetic profile. IVIVC made use to predict the bioavailability of the drug of particular dosage form. IVIVC is satisfactory for the therapeutic release profile specifications of the formulation. IVIVC model has capability to predict plasma drug concentration from in vitro dissolution media.

scholarly journals Peptide drugs for photopharmacology: how much of a safety advantage can be gained by photocontrol?

2020 ◽  
Vol 2 (1) ◽  
pp. FDD28 ◽  
Author(s):  
Oleg Babii ◽  
Sergii Afonin ◽  
Tim Schober ◽  
Liudmyla V Garmanchuk ◽  
Liudmyla I Ostapchenko ◽  
...  
Keyword(s):  
Chemotherapeutic Agent ◽  
In Vitro Cytotoxicity ◽  
Pharmacokinetic Parameters ◽  
Cancer Model ◽  
Pharmacokinetic Properties ◽  
Insight Into ◽  
Safety Advantage ◽  
Murine Cancer Model

Aim: To verify whether photocontrol of biological activity could augment safety of a chemotherapeutic agent. Materials & methods: LD50 values for gramicidin S and photoisomeric forms of its photoswitchable diarylethene-containing analogs were determined using mice. The results were compared with data obtained from cell viability measurements taken for the same compounds. Absorption, Distribution, Metabolism, and Elimination (ADME) tests using a murine cancer model were conducted to get insight into the underlying reasons for the observed in vivo toxicity. Results: While in vitro cytotoxicity values of the photoisomers differed substantially, the differences in the observed LD50 values were less pronounced due to unfavorable pharmacokinetic parameters. Conclusion: Despite unfavorable pharmacokinetic properties as in the representative case studied here, there is an overall advantage to be gained in the safety profile of a chemotherapeutic agent via photocontrol. Nevertheless, optimization of the pharmacokinetic parameters of photoisomers is an important issue to be addressed during the development of photopharmacological drugs.

scholarly journals In VitroDissolution andIn VivoBioavailability of Six Brands of Ciprofloxacin Tablets Administered in Rabbits and Their Pharmacokinetic Modeling

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Sahar Fahmy ◽  
Eman Abu-Gharbieh
Keyword(s):  
Pharmacokinetic Modeling ◽  
Pharmacokinetic Parameters ◽  
Noncompartmental Analysis ◽  
Dose Oral ◽  
Generic Products ◽  
Ensure Product Quality ◽  
Pharmacopoeial Requirements ◽  
Compartment Open Model

This study was undertaken to assess thein vitrodissolution andin vivobioavailability of six brands of ciprofloxacin oral tablets available in the UAE market using rabbits. Thein vitrodissolution profiles of the six ciprofloxacin products were determined using the USP dissolution paddle method. Pharmacokinetic modeling using compartmental and noncompartmental analysis was done to determine the pharmacokinetic parameters of ciprofloxacin after single-dose oral administration.In vitrorelease study revealed that the amount of ciprofloxacin released in 20 minutes was not less than 80% of the labeled amount which is in accordance with the pharmacopoeial requirements. All tested products are considered to be very rapid dissolving except for formulae A and D. Ciprofloxacin plasma concentration in rabbits was best fitted to a two-compartment open model. The lowest bioavailability was determined to be for product A (93.24%) while the highest bioavailability was determined to be for product E (108.01%). Postmarketing surveillance is very crucial to ensure product quality and eliminating substandard products to be distributed and, consequently, ensure better patient clinical outcome. The tested ciprofloxacin generic products distributed in the UAE market were proven to be of good quality and could be used interchangeably with the branded ciprofloxacin product.

scholarly journals Development and Evaluation of a Topical Anti-Inflammatory Preparation Containing Dodonaea polyandra Extract

2015 ◽  
Vol 18 (4) ◽  
pp. 578 ◽  
Author(s):  
Bradley S Simpson ◽  
Xianling Luo ◽  
Jiping Wang ◽  
Yunmei Song ◽  
David Claudie ◽  
...  
Keyword(s):  
Phase Separation ◽  
Human Skin ◽  
Dosage Form ◽  
Interleukin 1 ◽  
In Vitro Release ◽  
Skin Inflammation ◽  
Skin Model ◽  
Inflammation Model ◽  
Anti Inflammatory

Purpose: We have previously reported that the Australian Northern Kaanju (Kuuku I’yu) medicinal plant Dodonaea polyandra has anti-inflammatory activity. This is attributed largely to the presence of clerodane diterpenoids contained within the leaf resin. We envisaged developing a topical preparation to treat indications relating to skin inflammation. However, it was unknown whether the resin could be incorporated into a suitable dosage form while retaining the therapeutic value demonstrated in previous work. Therefore, the following study was undertaken to assess parameters of safety and efficacy for a prototype formulation containing the leaf resin extracted from D. polyandra. Methods: Using the assessment criteria of optimum appearance, tactile feeling, spreadability and odour, 78 different formulations were developed. Formulation stability was assessed using a centrifugal test with preparations displaying phase separation further modified or re-formulated. A prototype formulation containing 5% w/w plant resin was selected and subjected to in vitro release studies. This was quantified through HPLC analysis using two major bioactive diterpenoids as reference. The prototype formulation was tested for efficacy in a TPA-induced acute murine skin inflammation model as well as a 3D human skin model for irritancy/toxicity (Epiderm™). Results: The prototype resin cream was a chartreuse-coloured homogenous semisolid preparation that was readily spreadable upon contact with skin with no sensation of tackiness, residual greasiness, or irritation. The optimized cream showed no phase separation after 30 min centrifugation at 825 g. In the TPA-induced inflammation model, the resin formulation significantly reduced ear thickness and interleukin-1 beta levels in mouse ear tissue. The 5% w/w resin cream formulation showed no irritancy in a 3D human skin model. Conclusions: Our results demonstrate that bioactive resin from D. polyandra can be formulated into a stable and non-irritant semi-solid dosage form and reduce parameters of acute skin inflammation in vivo. 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 Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technology

2009 ◽  
Vol 59 (1) ◽  
pp. 15-30 ◽  
Author(s):  
Pramod Kumar ◽  
Sanjay Singh ◽  
Brahmeshwar Mishra
Keyword(s):  
Drug Release ◽  
Extended Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Tramadol Hydrochloride ◽  
Release Formulation ◽  
Extended Release Formulation

Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technologyExtended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media.In vivostudy was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax,tmax,AUC0-24,MRT) and relative bioavailability were calculated. Thein vitroandin vivoresults were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation.In vitro-in vivocorrelation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R= 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.

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