24 research outputs found
Core-in-cup/liquisol dual tackling effect on azelnidipine buccoadhesive tablet micromeritics, in-vitro release, and mucoadhesive strength
Reduced bioavailability of azelnidipine is related to its poor aqueous solubility and extensive first-pass metabolism, which hinder its efficacy. These problems were addressed by implementing (1) a liquisol technique for promoting the dissolution rate in a controlled-release manner and (2) a core-in-cup buccoadhesive drug delivery system as an alternative to the oral route. A 33 factorial design was used to study the effects of polymer type (sodium carboxymethyl cellulose (CMC Na), chitosan, or Carbomer P940) concentration (5, 10 or 15 %) and preparation technique (simple mix, liquisol or wet granulation) on the dissolution and mucoadhesion of core-in-cup azelnidipine buccoadhesive tablets. Tablet micromeritics, swelling index, mucoadhesive strength and in vitro release were characterized. Statistical analyses of these factors showed significant effects on the studied responses, where F#16 prepared by the liquisol technique and containing 15 % CMC Na was chosen with an overall desirability of 0.953
Gastroretentive raft liquid delivery system as a new approach to release extension for carrier-mediated drug
Gabapentin (GBP), an antiepileptic and anti-neuropathic agent, suffers from short half-life (5â7âh), has narrow absorption window, and is absorbed via carrier-mediated mechanism resulting in frequent dosing, poor compliance, and poor bioavailability (<60%). Moreover, GBP is a freely water-soluble drug, thus it is considered a challenging candidate to be formulated as extended release dosage form. In this study, raft forming systems were investigated as a potential drug delivery system for prolonging gastric residence time of GBP. A 23 full factorial design was adopted to study the effect of formulation variables (% gellan gum, % GMO, and % LM-pectin 101), on the percent of GBP released at different time intervals (1, 5, and 8âh) as well as the gel strength, and thus was achieved an optimized formula with zero-order release profile suitable for once-daily administration. In vivo assessment was performed in rats to evaluate gastric residence of the gel formed. In addition, the oral bioavailability of GBP relative to commercially available NeurontinÂź immediate release oral solution was also investigated. Significant increase was observed for Cmax, AUC(0ât), and AUC(0ââ). The increase in relative bioavailability of GBP from the optimized formula was 1.7 folds
Ultrahigh verapamil-loaded controlled release polymeric beads using superamphiphobic substrate: D-optimal statistical design, in vitro and in vivo performance
Controlled-release multiparticulate systems of hydrophilic drugs usually suffer from poor encapsulation and rapid-release rate. In the present study, ultra-high loaded controlled release polymeric beads containing verapamil hydrochloride (VP) as hydrophilic model drug were efficiently prepared using superamphiphobic substrates aiming to improve patient compliance by reducing dosing frequency. Superamphiphobic substrates were fabricated using clean aluminum sheets etched with ammonia solution and were treated with 1.5% (w/v) perfluorodecyltriethoxysilane (PFDTS) alcoholic solution. The effect of the main polymer type (lactide/glycolide (PLGA) 5004A, PLGA 5010, and polycaprolactone (PCL)), copolymer (Eudragit RS100) content together with the effect of drug load on encapsulation efficiency (EE%) and in vitro drug release was statistically studied and optimized via D-optimal statistical design. In vivo pharmacokinetic study was carried out to compare the optimized system relative to the market product (IsoptinÂź). Results revealed that superamphiphobic substrates were successfully prepared showing a rough micro-sized hierarchical structured surface upon observing with scanning electron microscope and were confirmed by high contact angles of 151.60â±â2.42 and 142.80°±05.23° for water and olive oil, respectively. The fabricated VP-loaded beads showed extremely high encapsulation efficiency exceeding 92.31% w/w. All the prepared systems exhibited a controlled release behavior with Q12âh ranging between 5.46 and 95.90%w/w. The optimized VP-loaded system composed of 150âmg (1.5% w/v) PCL without Eudragit RS100 together with 160âmg VP showed 2.7-folds mean residence time compared to the market product allowing once daily administration instead of three times per day
Olmesartan Medoxomil-Loaded Self-Nanoemulsifying Drug Delivery Systems: Design, In-Vitro Characterization, and Pharmacokinetic Assessments in Rabbits Via LC-MS/MS
Olmesartan medoxomil (OLM) is a lipophilic (log P = 4.31) antihypertensive drug suffering from limited oral bioavailability in humans (26%) due to its low aqueous solubility, uncontrolled enzymatic conversion to the active metabolite (olmesartan; OL) and efflux by drug resistance pumps. Surmounting such limitations via incorporation of OLM into self-nanoemulsifying drug delivery systems (SNEDDS). Based on OLM-equilibrium solubility studies in various oils, surfactants and co-surfactants, CapmulÂź MCM, TweenÂź 20, CremophorÂź EL and polyethylene glycol-400 (PEG) were combined in different ratios to plot ternary phase diagrams. OLM-loaded SENDDS were developed and evaluated for particle size, polydispersity index (PDI), zeta potential, self-emulsification time, morphology, drug released percentages after 5-min (Q5min%), 1-hour (Q1h%) and dissolution efficiency percentages (DE1h%). The OL pharmacokinetics from SNEDDS (F6) and BenicarÂź tablets were evaluated (LC-MS/MS) in rabbits. Spherical OLM-loaded SNEDDS were developed. The best-achieved SNEDDS (F6) showed short emulsification time (13 s), fine droplet size (60.00 nm), low PDI (0.25), negative zeta potential (-14.4 mV), promising dissolution parameters; Q5min% (29.78%), Q1h% (66.69%) and DE1h%(47.96%) and enhanced in vivo absorption characteristics; shorter Tmax, higher Cmax and larger AUC(0â48h; suggesting its potential for the enhancement of the oral absorption of practically insoluble drugs; like OLM
The Impact of Amorphisation and Spheronization Techniques on the Improved in Vitro & in Vivo Performance of Glimepiride Tablets
Purpose: Triple solid dispersion adsorbates (TSDads) and spherical agglomerates (SA) present new techniques that extensively enhance dissolution of poorly soluble drugs. The aim of the present study is to hasten the onset of hypoglycemic effect of glimepiride through enhancing its rate of release from tablet formulation prepared from either technique. Methods: Drug release from TSDads or SA tablets with different added excipients was explored. Scanning electron microscopy (SEM) and effect of compression on dissolution were illustrated. Pharmacodynamic evaluation was performed on optimized tablets. Results: TSDads & SA tablets with Cross Povidone showed least disintegration times of 1.48 and 0.5 min. respectively. Kinetics of drug release recorded least half-lives (54.13 and 59.83min for both techniques respectively). Cross section in tablets displayed an organized interconnected matrix under SEM, accounting for the rapid access of dissolution media to the tablet core. Components of tablets filled into capsules showed a similar release profile to that of tablets after compression as indicated by similarity factor. The onset time of maximum reduction in blood glucose in male albino rabbits was hastened to 2h instead of 3h for commercial tablets. Conclusion: After optimization of tablet excipients that interacted differently with respect to their effect on drug release, we could conclude that both amorphisation and spheronization were equally successful in promoting in vitro dissolution enhancement as well as providing a more rapid onset time for drug action in vivo
Superhydrophobic Substrates for Ultrahigh Encapsulation of Hydrophilic Drug into Controlled-Release Polyelectrolyte Complex Beads: Statistical Optimization and In Vivo Evaluation
In this work, ultrahigh drug-loaded chitosan (Ch)/K-carrageenan (Kc) polyelectrolyte complex (PEC) beads were formed in situ by cross-linking in a glutaraldehyde-saturated atmosphere and were prepared on superhydrophobic substrates fabricated by spraying glass surfaces with ready-made spray for domestic use (NeverWet®). Verapamil hydrochloride (VP), a highly hydrophilic drug with a short biological half-life, was incorporated into a series of Ch-based and/or Ch/Kc-PEC-based beads to control its release profile in vivo. The formulation of VP-loaded beads was optimized using stepwise statistical designs based on a prespecified criterion. Several characteristics of the prepared beads, such as entrapment efficiency (EE%), in vitro drug release, swelling ratio, size and surface microstructure as well as molecular interactions between the drug and formulation ingredients, were investigated. In vivo pharmacokinetic (PK) studies were carried out using the rabbit model to study the ability of the optimized VP-loaded beads to control the absorption rate of VP. Results revealed that the prepared superhydrophobic substrates were able to fabricate VP-loaded beads with extremely high EE exceeding 90% w/w compared to only 27.80% when using conventional ionotropic gelation technique. PK results showed that the rate of VP absorption was well controlled following oral administration of the optimized beads to six rabbits compared to a marketed VP immediate release (IR) tablet, as evidenced by a 2.2-fold increase in mean residence time (MRT) and 5.24-fold extension in half value duration (HVD) over the marketed product without any observed reduction in the relative oral bioavailability
Olmesartan medoxomil-loaded mixed micelles: Preparation, characterization and in-vitro evaluation
Olmesartan medoxomil (OLM) is highly lipophilic in nature (log p = 4.31) which attributes to its low aqueous solubility contributing to its low bioavailability 25.6%. OLM was loaded into mixed micelles carriers in a trial to enhance its solubility, thus improving its oral bioavailability. OLM-loaded mixed micelles were prepared, using a PluronicŸ mixture of F127 and P123, adopting the thin-film hydration method. Three drug: PluronicŸ mixture ratios (1:40, 1:50and 1: 60) and various F127: P123 ratios were prepared. OLM Loaded mixed micelles showed stability up to 12 h. The particle size of the systems varied from 364.00 nm (F3) to 13.73 nm (F18) with accepted Poly dispersity index (PDI) values. The in-vitro release studies of OLM from mixed micelles versus drug aqueous suspension were assessed using the reverse dialysis technique in a USP Dissolution tester apparatus (type II). The highest RE% (43%) was achieved with OLM-loaded mixed micelles (F8) when compared to (35%) of drug suspension
Comparative Pharmaceutical Study on Colon Targeted Micro-particles of Celecoxib: In-vitro- Invivo Evaluation
In order to target celecoxib which is a COX2 inhibitor, with potentials in the prevention and treatment of
colitis and colon cancer, it was formulated as microparticles using solvent /evaporation method and
various pH dependent Eudragit polymers .The in-vitro evaluation of the prepared microparticles showed
spherical and smooth morphology. The encapsulation efficiency and yield were high indicating that the
method used is simple and efficient at this scale. The in-vitro release study showed no release in acidic
medium for 2 hr followed by the release of the drug in pH 6.8 in case of Eudragit L100-55 and L100 and
pH 7.4 in case of Eudragit S100. The pharmacokinetic parameters were calculated and method
validation was performed to insure that it is suitable and reliable. . Pharmacokinetic parameters were
investigated by determining the Cmax, T max , AUC0-t, Kel , and T1/2 of the drug as a suspension and as
microparticles .There was a significant difference (P<0.05) in Tmax between the drug as a suspension
and as microparticles. The effect of celecoxib on the degree of inflammation was examined on acetic
acid induced colitis rat model and the drug was given as a suspension and as microparticles . The
evaluation was done using macroscopical,microscopical and biochemical examination. There was a
significant difference between the acetic acid control group and the treatment groups regarding all
examination criteria in the order microparticles formulated using Eudragit S100 followed by Eudragit
L100-55 while microparticles using Eudragit L100 and drug suspension showed almost the same results