Demonstration of Advanced Data Mining Tools for optimization of Pellets employing Modified Extrusion-Pelletization Technique

2020 ◽  
Vol 15 ◽  
Author(s):  
Hardika Rana ◽  
Mansi Dholakia ◽  
Mukesh Gohel ◽  
Abdelwahab Omri ◽  
Vaishali Thakkar ◽  
...  
Keyword(s):  
Data Mining ◽  
Drug Release ◽  
Physical Properties ◽  
Drug Dissolution ◽  
Pharmacokinetic Parameters ◽  
Compatibility Study ◽  
Distilled Water ◽  
Pregelatinized Starch ◽  
The Impact

Background: The multi particulate drug delivery system is preferred due to its numerous advantages but the batch to batch consistency and to achieve desired physical properties are the major challenges in the formulation of such dosage form. Objective: The objective of the present study was to explore the concept of quality by design for the development of galantamine HBr controlled release pellets using a modified palletization technique. Methods: Compritol 888 and Ethocel were chosen as hydrophobic release retardants while Avicel was chosen as pelletization aid. A compatibility study was conducted between the drug and excipients. Drug loaded extrudes were prepared by using a mixture of isopropyl alcohol, and dichloromethane. Before converting the wet extrudes in pellets, pregelatinized starch was sprinkled on them to improve the physical properties of the pellets. The pellets were characterized for size, shape, and flow. The critical evaluation parameter was the drug dissolution pattern in distilled water. The dissolution data were treated with advanced data mining techniques. The in-vivo profile was predicted employing pharmacokinetic parameters of the drug and in-vitro drug release data of optimized batch pellets. Results: The failure mode and effect analysis revealed that the amount of Compritol 888 ATO and Ethocel were the most critical formulation parameters. The results of FTIR and DSC revealed compatibility between the drug and the excipients. The spherical pellets exhibited good flow. The drug dissolution studies of the batches, prepared according to the central composite design, revealed modified drug release. Multiple regression analysis and analysis of variance were performed to identify statistically significant factors. Contour plots demonstrated the impact of the amount of Compritol 888 and ethyl cellulose. The Design-Expert software was used to identify optimized formulation. The predicted in-vivo plasma concentration-time profile revealed the modified drug release up to 12h. Conclusions: Compritol and Ethocel were able to retard the drug release up to 12 hrs in distilled water. The innovative finding of this study is the use of a dry binder (pregelatinized starch) to improve the characteristics of pellets. Other dry binders are expected to show a similar effect. The newer processing technique can be of use in the industry.

scholarly journals Development and in vitro Characterization of Gastro Retentive Raft Forming Stavudine Tablets

2017 ◽  
Vol 9 (01) ◽  
Author(s):  
Mahendar Rupavath ◽  
K. S. K Rao
Keyword(s):  
Drug Release ◽  
Matrix Tablets ◽  
Drug Dissolution ◽  
Release Mechanism ◽  
Compatibility Study ◽  
Drug Bioavailability ◽  
Drug Content ◽  
Weight Variation

The objective of the present investigation was to identify a suitable raft forming agent and to develop raft forming stavudine matrix tablets using different rate controlling natural, semi-synthetic and synthetic polymers to achieve prolonged gastric residence time, leading to an increase in drug bioavailability and patient compliance. Various raft forming agents were used in preliminary screening. Raft forming floating tablets were developed using pullulan gum as natural rate controlling polymer, and directly compressible grades of hydroxypropyl methylcellulose (Benecel K4M DC) as semi synthetic, and Carbopol 71G as synthetic rate controlling polymers respectively and optimum concentrations of sodium-bicarbonate as gas generating agent to generate optimum buoyancy by direct compression method. Raft forming tablets were evaluated for weight variation, thickness, hardness, friability, drug content, in vitro drug release, floating buoyancy and raft strength. Drug-excipients compatibility study showed no interaction between drug and excipients. Raft forming tablets showed satisfactory results when evaluated for weight variation, thickness, hardness, friability, drug content, and raft strength. The optimized formulation was selected based on physicochemical characteristics and in vitro drug dissolution characteristics. Further, the optimized formulation was evaluated for in vivo radiographic studies by incorporating BaSO4 as radio opaque substance. Optimized formulation showed controlled and prolonged drug release profiles while floating and raft formation over the dissolution medium. Diffusion followed by erosion with raft forming drug release mechanism was observed for the formulation, indicating that dissolution media diffusion and polymer erosion played an essential role in drug release. In vivo radiographic studies revealed that the raft forming formulations remained in the stomach for 240 30 min in rabbits and indicated that gastric retention time was increased by the floating and raft forming principle, which was considered and desirable for absorption window drugs.

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.

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 Gastroretentive Pulsatile Release Tablets of Lercanidipine HCl: Development, Statistical Optimization, andIn VitroandIn VivoEvaluation

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Gagganapalli Santhoshi Reddy ◽  
Usha Yogendra Nayak ◽  
Praful Balavant Deshpande ◽  
Srinivas Mutalik
Keyword(s):  
Blood Pressure ◽  
Drug Release ◽  
Immediate Release ◽  
Lag Time ◽  
Early Morning ◽  
Quadratic Model ◽  
Pharmacokinetic Parameters ◽  
Pulsatile Release

The present study was aimed at the development of gastroretentive floating pulsatile release tablets (FPRTs) of lercanidipine HCl to enhance the bioavailability and treat early morning surge in blood pressure. Immediate release core tablets containing lercanidipine HCl were prepared and optimized core tablets were compression-coated using buoyant layer containing polyethylene oxide (PEO) WSR coagulant, sodium bicarbonate, and directly compressible lactose. FPRTs were evaluated for variousin vitrophysicochemical parameters, drug-excipient compatibility, buoyancy, swelling, and release studies. The optimized FPRTs were testedin vivoin New Zealand white rabbits for buoyancy and pharmacokinetics. DoE optimization of data revealed FPRTs containing PEO (20% w/w) with coat weight 480 mg were promising systems exhibiting good floating behavior and lag time in drug release. Abdominal X-ray imaging of rabbits after oral administration of the tablets, confirmed the floating behavior and lag time. A quadratic model was suggested for release at 7th and 12th h and a linear model was suggested for release lag time. The FPRT formulation improved pharmacokinetic parameters compared to immediate release tablet formulation in terms of extent of absorption in rabbits. As the formulation showed delay in drug release bothin vitroandin vivo, nighttime administration could be beneficial to reduce the cardiovascular complications due to early morning surge in blood pressure.

Pharmacokinetic Profile of Oxaliplatin-Loaded pH-Responsive Hydrogels in Rabbits

2020 ◽  
Vol 26 (44) ◽  
pp. 5755-5763
Author(s):  
Kaleem Ullah ◽  
Shujaat Ali Khan ◽  
Muhammad Sohail ◽  
Abdul Mannan ◽  
Ghulam Murtaza
Keyword(s):  
Drug Release ◽  
Drug Loading ◽  
Oral Solution ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Platinum Compound ◽  
In Vivo Evaluation ◽  
Significant Difference

Background: Oxaliplatin (OXP), a 3rd generation platinum compound, which causes severe side effects due to; impulse high concentration in the bloodstream thereby exposing healthy cells at a high ratio, nonspecific delivery at the target site and non-compliance is administered intravenously. Objective: The project was aimed at the development, characterization, and in-vitro and in-vivo evaluation of pHresponsive hydrogels for oral administration of OXP. Methods: Hydrogel formulations were synthesized through a free radical polymerization technique followed by brief characterization using various techniques. The hydrogels were investigated for various in-vitro studies such as sol-gel, drug loading, swelling, drug release, and MTT-assay. While in-vivo studies such as oral tolerability, histopathology, and hematology studies were performed on rabbits. A simple and sensitive HPLC-UV method was optimized and the comparative pharmacokinetic study was performed in rabbits using OXP-oral solution and OXP-loaded hydrogels. Results: In-vitro characterization confirmed that the reactant was successfully crosslinked to form thermally stable hydrogels with decreased crystallinity and rough surface. Swelling and drug release showed that hydrogels were more responsive to basic pH (6.8 and 7.4) in comparison with pH 1.2. The blank hydrogels were cytocompatible as more than 95% of the cells were viable while free OXP and OXP-loaded hydrogels displayed dosedependent cytotoxic effect. In-vivo studies confirmed that chitosan and gelatin hydrogel suspension was well tolerable up to 3800 mg/kg and 4000 mg/kg of body weight, respectively. Hematology and serum chemistry reports were well within the range suggesting normal liver and kidney functions. Similarly, histopathology slides of rabbit vital organs were also found normal without causing any histopathological change. Conclusion: HPLC-UV method was successfully optimized for OXP detection in oral solution and hydrogels administered to rabbits. A significant difference was found among various pharmacokinetic parameters by comparing the two groups including half-life (t1/2), tmax, Cmax, AUCtot MRT, Vz, and Lz.

scholarly journals Formulation and Physicochemical Characterization of Cyclosporine Microfiber by Electrospinning

2019 ◽  
Vol 9 (2) ◽  
pp. 249-254
Author(s):  
Shahla Mirzaeei ◽  
Ghobad Mohammadi ◽  
Navid Fattahi ◽  
Pardis Mohammadi ◽  
Ali Fattahi ◽  
...  
Keyword(s):  
Drug Release ◽  
Physicochemical Properties ◽  
Dissolution Rate ◽  
Water Soluble ◽  
Crystalline Lattice ◽  
Drug Dissolution ◽  
Absolute Bioavailability ◽  
Study Results ◽  
Pure Drug

Purpose: The objective of this study was to improve the permeability and water solubility rate of a poor water soluble drug, cyclosporine A (CsA). Methods: In order to improve the drug dissolution rate and oral bioavailability, electrospinning method was used as an approach to prepare. The fibers were evaluated for surface morphology, thermal characterizations, drug crystallinity, in vitro drug release and in vivo bioavailability studies. Results: Scanning electron microscope (SEM) results confirmed that the fibers were in microsize range and the size of the fibers was in the rang of 0.2 to 2 micron. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (XRPD) analysis ensured that the crystalline lattice of drug were weakened or destroyed in the fibers. The drug release was 15.28%, 20.67%, and 32.84% from pure drug, fibers of formulation B, and formulation A, respectively. In vivo study results indicated that the bioavailability parameters of the optimized fiber formulation were improved and the maximum concentration (Cmax) were significantly higher for fibers (3001 ng/mL) than for pure drug (2550 ng/mL). The dissolution rate of the formulations was dependent on the nature and ratio of drug to carriers. Conclusion: The physicochemical properties showed that the optimized mixture of polyethylene glycol (PEG) and povidone (PVP) fibers could be an effective carrier for CsA delivery. PEG and PVP fibers improved the absolute bioavailability and drug dissolution rate with appropriate physicochemical properties.

DESIGN OF PRONIOSOMAL GEL CONTAINING EUGENOL AS AN ANTIFUNGAL AGENT FOR THE TREATMENT OF ORAL CANDIDIASIS

INDIAN DRUGS ◽  
2018 ◽  
Vol 55 (09) ◽  
pp. 55-57
Author(s):  
T. S Vishnu ◽  
◽  
A. Dubey ◽  
G.S Ravi ◽  
S. Hebbar
Keyword(s):  
Antifungal Activity ◽  
Drug Release ◽  
Release Kinetics ◽  
Oral Candidiasis ◽  
In Vivo Studies ◽  
Compatibility Study ◽  
In Vitro Drug Release ◽  
Release Study

The objective of this study was to design and investigate the antifungal activity of proniosomal gel of eugenol for the treatment of oral candidiasis. The proniosomal gel was prepared by coacervation phase separation method using different surfactants like spans 20, 60, 80, soya lecithin and cholesterol. The proniosomal gel formulations were evaluated for visual inspection, pH detection, viscosity, spreadability, in vitro drug release and kinetics study, and in vivo studies. The compatibility study indicated that the drug and the excipients were compatible with each other. The results showed that pH, viscosity and spreadability were all acceptable for topical preparation. In vitro drug release study and drug release kinetics were conducted to check the release study and drug release patterns of the formulation. Amongst the formulations, an optimized formulation was selected to conduct an in vivo study. Candida albicans was used to induce oral candidiasis for the evaluation of therapeutic efficacy of proniosomal gel in immunosuppressed rats. Activity was analysed by microbiological and histopathological techniques and was compared with the marketed product. It is evident from the study that the proniosomal gel shows sustained release trend with strong antifungal activity.

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 Advances in drug release investigations: Trends and developments for dissolution test media

2020 ◽  
Vol 90 (4) ◽  
pp. 155-169
Author(s):  
Melinda Kakuk ◽  
Dóra Farkas ◽  
István Antal ◽  
Nikolett Kállai-Szabó
Keyword(s):  
Drug Release ◽  
Pharmaceutical Formulations ◽  
Oral Dosage ◽  
Drug Dissolution ◽  
Biorelevant Media ◽  
Biologically Relevant ◽  
Stability Issues ◽  
Oral Dosage Forms

Dissolution research started more than a century ago in the field of physical chemistry and went through several significant developments since. Yet, the explicit attention in drug-related dissolution has only started growing in the 1950s, after the researchers realized that drug release from orally administered solid pharmaceutical formulations significantly influences the bioavailability. Researches show that solubility and permeability of the drugs are key factors in the correlation between the in vitro examination and the in vivo determinations (IVIVC). This review aims to summarize the most relevant developments in chronological order, ranging from simple disintegration studies to biorelevant methods. Biorelevant methods can be used to recognize the effects of food on dissolution, as well as to identify solubility limitations and stability issues. The development of a biologically relevant dissolution method for oral dosage forms needs to take the physiological conditions of the gastrointestinal (GI) tract into account that may influence the drug dissolution. This review presents the simplest dissolution media, the composition of biorelevant media simulating gastrointestinal fluids, and the latest updates of the field.

scholarly journals Impact of the C2/C6 Ratio of High-molecular-weight Hydroxyethyl Starch on Pharmacokinetics and Blood Coagulation in Pigs

2007 ◽  
Vol 107 (3) ◽  
pp. 442-451 ◽  
Author(s):  
Sebastian Schramm ◽  
Caroline Thyes ◽  
Philippe Frascarolo ◽  
Thierry Buclin ◽  
Marco Burki ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Blood Coagulation ◽  
High Molecular Weight ◽  
Hydroxyethyl Starch ◽  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Two Compartment Model ◽  
The Impact

Background High-molecular-weight, low-substituted hydroxyethyl starch (HES) may not affect blood coagulation more than low-molecular-weight, low-substituted HES. The authors assessed in vivo the effect of a lowered C2/C6 ratio on pharmacokinetic characteristics and the impact on blood coagulation of high-molecular-weight, low-substituted HES. Methods A prospective, randomized, parallel study in 30 pigs compared HES 650/0.42/2.8 with HES 650/0.42/5.6. Before, during, and after infusion of 30 ml/kg body weight HES, blood samples were collected over 630 min to measure HES concentrations and plasmatic coagulation and to assess blood coagulation in whole blood by Thrombelastography (TEG; Haemoscope Corporation, Niles, IL). Pharmacokinetic parameters were estimated using a two-compartment model. Results The elimination constant was 0.009 +/- 0.001 min(-1) for HES 650/0.42/2.8 and 0.007 +/- 0.001 min(-1) for HES 650/0.42/5.6 (P < 0.001); the area under the plasma concentration-time curve was 1,374 +/- 340 min x g/l for HES 650/0.42/2.8 and 1,697 +/- 411 min x g/l for HES 650/0.42/5.6 (P = 0.026). The measured plasma HES concentrations were not different between HES 650/0.42/2.8 and HES 650/0.42/5.6. Both HES solutions equally affected blood coagulation: Thrombelastographic coagulation index decreased similarly at the end of infusion of HES 650/0.42/2.8 and at the end of infusion of HES 650/0.42/5.6 (P = 0.293). Also, activated partial thromboplastin and prothrombin times increased similarly for HES 650/0.42/2.8 and HES 650/0.42/5.6 (P = 0.831). Conclusion Reducing the C2/C6 ratio in high-molecular, low-substituted HES solutions results in a slightly faster HES elimination. However, the blood coagulation compromising effect was unaffected.

Sign in / Sign up

Export Citation Format

Share Document