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 (5–7 h), 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 8 h) 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 Neurontin® immediate release oral solution was also investigated. Significant increase was observed for Cmax, AUC(0–t), and AUC(0–∞). 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 (Isoptin®). 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 151.60 ± 2.42 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 Q12 h ranging between 5.46 and 95.90%w/w. The optimized VP-loaded system composed of 150 mg (1.5% w/v) PCL without Eudragit RS100 together with 160 mg VP showed 2.7-folds mean residence time compared to the market product allowing once daily administration instead of three times per day

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&reg;). 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

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

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 Pluronic® mixture of F127 and P123, adopting the thin-film hydration method. Three drug: Pluronic® 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

Facile development, characterization, and optimization of new metformin-loaded nanocarrier system for efficient colon cancer adjunct therapy

<p><b>Purpose:</b> Metformin hydrochloride (MF) repurposing as adjuvant anticancer therapy for colorectal cancer (CRC) proved effective. Several studies attempted to develop MF-loaded nanoparticles (NPs), however the entrapment efficiency (EE%) was poor. Thus, the present study aimed at the facile development of a new series of chitosan (CS)-based semi-interpenetrating network (semi-IPN) NPs incorporating Pluronic^® nanomicelles as nanocarriers for enhanced entrapment and sustained release of MF for efficient treatment of CRC.</p> <p><b>Methods:</b> The NPs were prepared by ionic gelation and subsequently characterized using FTIR, DSC, TEM, and DLS. A full factorial design was also adopted to study the effect of various formulation variables on EE%, particle size, and zeta-potential of NPs.</p> <p><b>Results:</b> NPs had a spherical shape and a mean particle size ranging between 135 and 220 nm. FTIR and DSC studies results were indicative of successful ionic gelation with the drug being dispersed in its amorphous form within CS-Pluronic^® matrix. Maximum EE% reaching 57.00 ± 12.90% was achieved using Pluronic^®-123 based NPs. NPs exhibited a sustained release profile over 48 h. The MF-loaded NPs sensitized RKO CRC cells relative to drug alone.</p> <p><b>Conclusion:</b> The reported results highlighted the novel utility of the developed NPs in the arena of colon cancer treatment.</p

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 bucco-adhesive 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 show ed 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

Zero-order release and bioavailability enhancement of poorly water soluble Vinpocetine from self-nanoemulsifying osmotic pump tablet

<p>Solid self-nanoemulsifying (S-SNEDDS) asymmetrically coated osmotic tablets of the poorly water-soluble drug Vinpocetine (VNP) were designed. The aim was to control the release of VNP by the osmotic technology taking advantage of the solubility and bioavailability-enhancing capacity of S-SNEDDS. Liquid SNEDDS loaded with 2.5 mg VNP composed of Maisine™ 35-1, Transcutol^® HP, and Cremophor^® EL was adsorbed on the solid carrier Aeroperl^®. S-SNEDDS was mixed with the osmotic tablet excipients (sodium chloride, Avicel^®, HPMC-K4M, PVP-K30, and Lubripharm^®), then directly compressed to form the core tablet. The tablets were dip coated and mechanically drilled. A 3²*2¹ full factorial design was adopted. The independent variables were: type of coating material (<i>X</i>₁), concentration of coating solution (<i>X</i>₂), and number of drills (<i>X</i>₃). The dependent variables included % release at 2 h (<i>Y</i>₁), at 4 h (<i>Y</i>₂), and at 8 h (<i>Y</i>₃). The <i>in vivo</i> performance of the optimum formula was assessed in rabbits. Zero-order VNP release was obtained by the single drilled 1.5% Opadry^® CA coated osmotic tablets and twofold increase in VNP bioavailability was achieved. The combination of SNEDDS and osmotic pump tablet system was successful in enhancing the solubility and absorption of VNP as well as controlling its release.</p