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.
Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various fields such as pharmaceuticals, biomaterials, agriculture, food, water purification. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45-2mm in size, was fully characterized. Results showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45-2mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.
Solid oral dosage forms (SODF) are drug vehicles commonly prescribed by physicists in primary and secondary cares, as they are the most convenient for the patient and facilitate therapy management. Concerns regarding unintended adhesion of SODF during oro-esophageal transit remain, especially in multimorbid patients, bedridden patients and patients suffering from dysphagia. Hence, this factor should be considered during the development of SODF, and more attention should be given on the design of appropriate surface conditions considering patients with swallowing problems. The aim of this work was to estimate the low mucoadhesion strength of different pharmaceutical polymers frequently used in coating technologies, since this property is thought to have impact on the mucoadhesive profile of SODF during oro-esophageal transit. In an approach using in vitro methods based on particle interactions, polyethylene glycol grades (PEG) showed the lowest interaction forces suggesting a more favorable in vivo performance than hydroxypropyl methylcellulose (HPMC), which was found to have the highest particle interaction. Preference should be given to coating formulations with lower concentrations of polymer and grades with low molecular weight. In addition, rheological measurements should be adopted when targeting poor mucoadhesive polymers.
Drop-on-demand inkjet printing is a potential enabling technology both for continuous manufacturing of pharmaceuticals and for personalized medicine, but its use is often restricted to low-viscosity solutions and nano-suspensions. In the present study, a robust electromagnetic (valvejet) inkjet technology has been successfully applied to deposit prototype dosage forms from solutions with a wide range of viscosities, and from suspensions with particle sizes exceeding 2 μm. A detailed solid-state study of paracetamol, printed from a solution ink on hydroxypropyl methylcellulose (HPMC), revealed that the morphology of the substrate and its chemical interactions can have a considerable influence on polymorphic selectivity. Paracetamol ink crystallized exclusively into form II when printed on a smooth polyethylene terephthalate substrate, and exclusively into form I when in sufficient proximity to the rough surface of the HPMC substrate to be influenced by confinement in pores and chemical interactions. The relative standard deviation in the strength of the dosage forms was <4% in all cases, for doses as low as 0.8 mg, demonstrating the accuracy and reproducibility associated with electromagnetic inkjet technology. Good adhesion of indomethacin on HPMC was achieved using a suspension ink with hydroxypropyl cellulose, but not on an alternative polyethylene terephthalate substrate, emphasising the need to tailor the binder to the substrate. Future work will focus on lower-dose drugs, for which dosing flexibility and fixed dose combinations are of particular interest.
The aim of this study was to prepare and evaluate ion-activated in-situ gel ophthalmic drug delivery system based on kappa-carrageenan (KC), using acyclovir as a model drug, hydroxypropyl methylcellulose (HPMC) as the viscosity agent and hydroxypropyl-β-cyclodextrin (HP-β-CD) as the penetration enhancer. The two ternary phase diagrams exhibited the effect of K+ and Ca2+ on the sol-to-gel transition, which turned out that KC was more sensitive to K+. The optimal ophthalmic matrix (prepared from KC and HPMC) was optimized with in-vitro drug release test. The apparent permeability coefficient of acyclovir under 2% HP-β-CD was found to have dramatically increased (2.16-ploid) than that of conventional eye drops (P < 0.05). The ion-activated in-situ gel based on KC significantly delayed drug release and its bioavailability could be improved in comparison with the conventional eye drops. Hence, it has the potential to be a novel kind of ocular drug delivery system.