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

Bioadhesive Controlled Metronidazole Release Matrix Based on Chitosan and Xanthan Gum

Metronidazole, a common antibacterial drug, was incorporated into a hydrophilic polymer matrix composed of chitosan xanthan gum mixture. Hydrogel formation of this binary chitosan-xanthan gum combination was tested for its ability to control the release of metronidazole as a drug model. This preparation (MZ-CR) was characterized by in vitro, ex vivo bioadhesion and in vivo bioavailability study. For comparison purposes a commercial extended release formulation of metronidazole (CMZ) was used as a reference. The in vitro drug-release profiles of metronidazole preparation and CMZ were similar in 0.1 M HCl and phosphate buffer pH 6.8. Moreover, metronidazole preparation and CMZ showed a similar detachment force to sheep stomach mucosa, while the bioadhesion of the metronidazole preparation was higher three times than CMZ to sheep duodenum. The results of in vivo study indicated that the absorption of metronidazole from the preparation was faster than that of CMZ. Also, MZ-CR leads to higher metronidazole Cmax and AUC relative to that of the CMZ. This increase in bioavailability might be explained by the bioadhesion of the preparation at the upper part of the small intestine that could result in an increase in the overall intestinal transit time. As a conclusion, formulating chitosan-xanthan gum mixture as a hydrophilic polymer matrix resulted in a superior pharmacokinetic parameters translated by better rate and extent of absorption of metronidazole

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

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, Capmul® MCM, Tween® 20, Cremophor® 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 Benicar® 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(0−48h; suggesting its potential for the enhancement of the oral absorption of practically insoluble drugs; like OLM

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

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

An <i>in vivo</i> study of <i>Hypericum perforatum</i> in a niosomal topical drug delivery system

<p>The active compounds present in <i>Hypericum perforatum</i> L. (Hypericaceae) include hyperforin, hypericins and flavonoids, which are assumed to be responsible for the activity of the extract in the treatment of wounds and scars. The present study aimed to incorporate <i>H. perforatum</i> extract standardized to a known content of phloroglucinols, naphthodianthrones and polyphenolic compounds into an effective transdermal drug delivery system capable of entrapping both lipophilic and hydrophilic constituents in the form of niosomal gels for wound treatment. An 80% ethanol extract (HE) was prepared on a pilot scale using DIG-MAZ. An HPLC-DAD holistic profile was established for HE and was standardized to contain 3.4 ± 4 rutin, 1.1 ± 3 chlorogenic acid, 0.5 ± 2 quercitrin, 2.8 ± 2 hyperforin, and 0.51 ± 3% w/w total hypericins. Niosomes were prepared using the modified reverse phase evaporation technique (REV). The wound healing effect of the gel was tested on 16 adult mongrel dogs. A significant decrease in the inflammatory cell count (18.4 ± 5.3) was recorded in the niosomal gel 1.5% NaCMC-treated group at the 7th day post wounding. It induced a marked regression in the inflammatory phase and enhanced the early beginning of the proliferative phase of wound healing. After 21 days, it showed complete re-epithelization, formation of new matrix fibers and significant reduction in the wound size, compared to the control and the Panthenol® 2% cream treated groups. This is the first study of <i>H. perforatum</i> in a niosomal topical drug delivery system.</p