Concept: Methyl cellulose
The present investigation was carried out to formulate and optimize the bioerodable insert of Azithromycin in order to prolong the release time and improve the ocular availability in ophthalmic infections. A modified solvent casting method was used for the preparation of azithromycin insert in which hydroxyl propyl methyl cellulose (HPMC) and Eudragit RL100 were used as drug reservoir and rate controlling membrane respectively. Thereafter the, formulations were evaluated for the uniformity of thickness and weight, surface pH, folding endurance, percentage moisture loss, percentage moisture absorption, drug content, in-vitro release, kinetics studies (zero order, first order, Higuchi and Korsmeyer - Peppas model) and stability studies. The Formulation H8 (amongst the range of H1-H10) ,comprising of 1.5% HPMC and 3% Eudragit RL100 ,was found to be optimized formulation on the basis of uniformity of thickness (0.26 ± 0.004 mm) and weight (24.9 ± 0.27 mg), surface pH (7.1 ± 0.063), folding endurance (18.3 ± 0.81), percentage moisture loss (7.49 ± 0.30%), percentage moisture absorption (5.7%), drug content (1.98 mg ), in-vitro release (99%) , stability studies (Shelf life- 346 days) and better ocular tolerability. The formulation H8 showed a steady and controlled release of the drug over a 12 hour period with non-Fickian diffusion release mechanism, compared to a normal release period of 2-3 hours. The optimized insert showed promising results and can be used to treat a wide range of ocular infections.
The objective of this study was to investigate the effect of polymeric microcarriers on the in-vivo intranasal uptake of an anti-migraine drug for brain targeting. Mucoadhesive powder formulations consisted of antimigraine drug, zolmitriptan, and chitosans (various molecular weights and types) or hydroxypropyl methylcellulose (HPMC). Their suitability for nasal administration was evaluated by in-vitro and ex-vivo mucoadhesion and permeation tests. The formulations based on chitosan glutamate (CG) or HPMC were tested in-vivo because they showed good mucoadhesive properties and altered the permeation rate of the drug. The in-vivo results from intravenous infusion and nasal aqueous suspension of the drug or nasal particulate powders were compared. The plasmatic AUC values obtained within 8 h following intravenous administration appeared about three times higher than those obtained by nasal administration, independent of the formulations. Zolmitriptan concentrations in the cerebrospinal fluid obtained from nasal and intravenous administrations were respectively 30 and 90 times lower than the concentrations of the drug in the blood. Thus, nasal administration potentiated the central zolmitriptan activity allowing a reduction of the drug peripheral levels, with respect to the intravenous administration. Among nasally administered formulations, CG microparticles showed the highest efficacy in promoting the central uptake of zolmitriptan within 1 h.
Abstract Context: Buspirone HCl has very low oral bioavailability (4%) due to deactivation by extensive first pass effect. It also has very limited transdermal permeation due to its high hydrophilicity. Objective: The aim of this study was to increase the transdermal permeation of buspirone HCl utilizing a stable dosage form. Methods: Transfersomes were prepared using Tween-80 as a flexibility imparting agent to the vesicular walls. Oleic acid and/or ethanol, with different percentages, were utilized as a permeation enhancer. Formulations were characterized by analyzing particle size, polydispersity index, zeta potential, entrapment efficiency, in vitro release and ex vivo drug permeation. Factorial design (3(2)) was planned for the optimization of formulations using Design-Expert® software. Lyophilized transfersomal gel of the optimized formulation was prepared using hydroxypropyl methylcellulose (HPMC) K100, carboxymethyl cellulose or sodium alginate with or without mannitol as a cryoprotectant. Physical characterization of the transfersomes and the lyophilized gel were carried out using transmission and scanning electron microscopy, respectively. Results: The optimized formulation (T7), containing 35% oleic acid, had the highest desirability value (0.658) with high ex vivo drug flux (43.40 µg/h/cm(2)) through rat skin when compared with the aqueous drug solution and formula T1 (without oleic acid). The T7 transfersomal gel containing HPMC K100 (G2) had the highest desirability value (0.640) among the lyophilized gel formulations with decreased ex vivo drug flux (38.98 µg/h/cm(2)) in comparison with the original transfersomal formula (T7). Conclusions: Lyophilized transfersomal gel containing oleic acid was considered as a promising transdermal delivery system for hydrophilic drugs.
: We report 2 cases of a foreign body reaction to Radiesse, a semipermanent soft-tissue filler consisting of 30% calcium hydroxylapatite microspheres and 70% carboxymethyl cellulose gel carrier. In one case, injection of this filler provoked a nodule on the columella, which was discovered during rhinoplasty. In the second case, the reaction was revealed during histopathologic examination of the deep section of a surgically removed basal-cell carcinoma. Histopathology showed a foreign body reaction with numerous giant cells and histiocytes, some plasma cells, and lymphocytes. Within this inflammatory reaction, a nonpolarizing exogenous material was identified consisting of numerous, round, uniformly sized, yellowish, extracellular deposits with a crackled appearance. Although many authors claim that Radiesse does not induce any foreign body reactions, we found a number of similar histopathologic pictures in studies describing animal or human auricular area test sites or even in reports of lip nodules, which are a well-known adverse effect after injection of this filler into this site. The histopathologic appearance of Radiesse is particularly distinctive and easily recognizable by dermatologists and dermatopathologists.
Laminar extrusion of wet masses was studied as a novel technology for the production of dosage forms for oral drug delivery. Extrusion was carried out with a ram extruder. Formulations contained either microcrystalline cellulose (MCC) or dicalcium phosphate (DCP) as diluent, hydroxypropyl methylcellulose (HPMC), lactose and water. Extrudates were characterized for their tensile strength, Young’s modulus of elasticity, water absorption, gel forming capacity and release of two model drugs, coumarin (COU) and propranolol hydrochloride (PRO). Cohesive extrudates could be produced with both filling materials (MCC and DCP) when HPMC was included as a binder at low amounts (3.3-4.5% w/w dry weight). Employing more HPMC, the elasticity of the wet masses increased which resulted in distinct surface defects. For MCC, the maximum HPMC amount that could be included in the formulations (15% w/w dry weight) did not affect the mechanical properties or decrease the drug release significantly. For DCP extrudates, the maximally effective HPMC amount was 30% (w/w dry weight) with influence on both the mechanical properties and drug release. This study suggests that laminar extrusion of wet masses is a feasible technique for the production of dosage forms for oral drug delivery.
This work aims to prepare sustained release buccal mucoadhesive tablets of buspirone hydrochloride (BH) to improve its systemic bioavailability. The tablets were prepared according to 5×3 factorial design where polymer type was set at five levels (carbopol, hydroxypropyl methylcellulose, sodium alginate, sodium carboxymethyl cellulose and guar gum), and polymer to drug ratio at three levels (1:1, 2:1 and 3:1). Mucoadhesion force, ex-vivo mucoadhesion time, percent BH released after 8h (Q8h) and time for release of 50% BH (T50%) were chosen as dependent variables. Additional BH cup and core buccal tablets were prepared to optimize BH release profile and make it uni-directional along with the tablets mucoadhesion. Tablets were evaluated in terms of content uniformity, weight variation, thickness, diameter, hardness, friability, swelling index, surface pH, mucoadhesion strength and time and in-vitro release. Cup and core formula (CA10) was able to adhere to the buccal mucosa for 8h, showed the highest Q8h (97.91%) and exhibited a zero order drug release profile. Pharmacokinetic study of formula CA10 in human volunteers revealed a 5.6 fold increase in BH bioavailability compared to the oral commercial Buspar(®) tablets. Conducting level A in-vitro/in-vivo correlation showed good correlation (r(2)= 0.9805) between fractions dissolved in-vitro and fractions absorbed in-vivo.
The aim of this study was to develop hydroxypropyl methyl cellulose (HPMC)/chitosan gel containing polymeric micelles loaded with simvastatin (Sim) and evaluates its wound healing properties in rats. An irregular full factorial design was employed to evaluate the effects of various formulation variables including polymer/drug ratio, hydration temperature, hydration time and organic solvent type on the physicochemical characteristics of pluronic F127-cholesterol nanomicelles prepared using the film hydration method. Among single studied factors, solvent type had the most impact on the amount of drug loading and zeta potential. Particle size and release efficiency was more affected by hydration temperature. The optimized formulation suggested by desirability of 93.5% was prepared using 1 mg of Sim, 10 mg of copolymer, dichloromethane as the organic solvent, hydration time of 45 min and hydration temperature of 25(°) C. The release of the drug from nanomicelles was found to be biphasic and showed a rapid release in the first stage followed by a sustained release for 96 h. The gel-contained nanomicelles exhibited pseudo-plastic flow and more sustained drug release profile compared to nanomicelles. In excision wound model on normal rats, the wound closure of the group treated by Sim loaded micelles-gel was superior to other groups. Taken together, Sim loaded micelles -gel may represent a novel topical formulation for wound healing.
Three dimensional (3D) extrusion-based printing is a paste-based rapid prototyping process, which is capable of building complex 3D structures. The aim of this study was to explore the feasibility of 3D extrusion-based printing as a pharmaceutical manufacture technique for the fabrication of gastro-floating tablets. Novel low-density lattice internal structure gastro-floating tablets of dipyridamole were developed to prolong the gastric residence time in order to improve drug release rate and consequently, improve bioavailability and therapeutic efficacy. Excipients commonly employed in the pharmaceutical study could be efficiently applied in the room temperature 3D extrusion-based printing process. The tablets were designed with three kinds of infill percentage and prepared by hydroxypropyl methylcellulose (HPMC K4M) and hydroxypropyl methylcellulose (HPMC E15) as hydrophilic matrices and microcrystalline cellulose (MCC PH101) as extrusion molding agent. In vitro evaluation of the 3D printed gastro-floating tablets was performed by determining mechanical properties, content uniformity, and weight variation. Furthermore, re-floating ability, floating duration time, and drug release behavior were also evaluated. Dissolution profiles revealed the relationship between infill percentage and drug release behavior. The results of this study revealed the potential of 3D extrusion-based printing to fabricate gastro-floating tablets with more than 8h floating process with traditional pharmaceutical excipients and lattice internal structure design.
Concomitant ingestion of alcohol and medications can greatly affect drug plasma concentrations as dose dumping or failure may occur as a result of the fact that formulation excipients may not always be resistant to alcohol. In this study, a natural polysaccharide (Sesamum radiatum gum) (SG) was extracted, characterized and used to formulate sustained release theophylline compacts to study the effect of varying alcohol concentrations (v/v) in dissolution media on drug release from these compacts. X-ray powder diffraction showed that the extracted gum was amorphous in nature with the powder having excellent compaction properties as observed with its compact being significantly harder than those prepared with pure hydroxypropyl methyl cellulose (HPMC) K4M. X-ray microtomography showed that the compacts produced were homogenous in nature, however, swelling studies showed failure of the compacts at the highest concentration of absolute ethanol used (40% v/v). Dissolution studies showed similarity at all levels of alcohol tested (f2 = 57-91) in simulated gastric (0.1 N HCl, pH 1.2) and intestinal fluids (phosphate buffer, pH 6.8) for the HPMC compacts whereas dissimilarity only occurred for the SG compacts at the highest alcohol concentration in both media (f2 = 35). The suitability of SG as a matrix former that can resist alcoholic effects therefore makes it suitable as an alternative polymer with wider applications for drug delivery.
Here, the mesoporous silica (Sylysia 350) was selected as mesoporous material, hydroxypropyl methylcellulose (HPMC) was selected as crystallization inhibitor, and febuxostat (FBT) was selected as model drug, respectively. The FBT-Sylysia-HPMC nanomatrix (FBT@SHN) was prepared. The characteristics of FBT@SHN were investigated in vitro and in vivo. Our results indicated that the FBT in FBT@SHN was in amorphous form. The solubility and dissolution of FBT in FBT@SHN were significantly increased. The oral bioavailability of FBT in FBT@SHN was greatly improved 5.8-fold compared with that in FBT suspension. This nanomatrix could be used as a drug delivery platform for improving the oral bioavailability.