F. S. Habib

Liposomes as an ocular delivery system of fluconazole: in-vitro studies

Acta Ophthalmol. 2010: 88: 901–904

Dissolution Rates of Carbamazepine and Nitrazepam Utilizing Sugar Solid Dispersion System

AbstractThe dissolution of carbamazepine and nitrazepam from Its solid dispersions using anhydrous lactose, mannitol, galactose, PEG 6000 and coprecipitate using polyvinylpyrrolidone (PVP) 40,000 was investigated. The dissolution process of capsules containing either carbamazepine or nitrazepam as solid dispersion or coprecipitate followed an apparent first order process. The combination of carbamazepine with sugars (mannitol, lactose, and galactose) caused, in every case, an increase in the dissolution rate of the drug. Carbamazepine-PVP coprecipitate gave the higher dissolution rate than that of the solid dispersions with sugars and PEG 6000. Nitrazepam-lactose system gave higher dissolution rate than the other dispersions and coprecipitate. This enhancement in dissolution rate was much more obvious for the solid dispersions and coprecipitate than for the physical mixtures.

From The Mine to Cancer Therapy: Natural and Biodegradable Theranostic Silicon Nanocarriers from Diatoms for Sustained Delivery of Chemotherapeutics

Drug delivery using synthetic nanoparticles including porous silicon has been extensively used to overcome the limitations of chemotherapy. However, their synthesis has many challenges such as lack of scalability, high cost, and the use of toxic materials with concerning environmental impact. Nanoscale materials obtained from natural resources are an attractive option to address some of these disadvantages. In this paper, a new mesoporous biodegradable silicon nanoparticle (SiNP) drug carrier obtained from natural diatom silica mineral available from the mining industry is presented. Diatom silica structures are mechanically fragmented and converted into SiNPs by simple and scalable magnesiothermic reduction process. Results show that SiNPs have many desirable properties including high surface area, high drug loading capacity, strong luminescence, biodegradability, and no cytotoxicity. The in-vitro release results from SiNPs loaded with anticancer drugs (doxorubicin) demonstrate a pH-dependent and sustained drug release with enhanced cytotoxicity against cancer cells. The cells study using doxorubicin loaded SiNPs shows a significantly enhanced cytotoxicity against cancer cells compared with free drug, suggesting their considerable potential as theranostic nanocarriers for chemotherapy. Their low-cost manufacturing using abundant natural materials and outstanding chemotherapeutic performance has made them as a promising alternative to synthetic nanoparticles for drug delivery applications.

Effect of Particle Size on the Dissolution Rate of Monophenylbutazone Solid Dispersion in Presence of Certain Additives

AbstractMonophenylbutazone is a very sparingly soluble drug. The effect of particle size on the dissolution characteristics of monophenylbutazone in a dissolution medium of 0.1 N hydrochloric acid and 0.1 N hydrochloric acid to which was added 0.005% Tween 80, was carried out. The enhancement of the dissolution rate of the medicament was attained by formulating the drug in both solid dispersion and physical mixture using urea and polyethylene glycol 4000 as carriers. A comparative dissolution behaviour of the medicament in different solid dispersion and physical mixture ratios were investigated at particle, size of < 63 μ. Drug-urea solid dispersion of a ratio 5:95% produced the highest dissolution rate.

Stability and magnetically induced heating behavior of lipid-coated Fe3O4 nanoparticles

Magnetic nanoparticles that are currently explored for various biomedical applications exhibit a high propensity to minimize total surface energy through aggregation. This study introduces a unique, thermoresponsive nanocomposite design demonstrating substantial colloidal stability of superparamagnetic Fe3O4 nanoparticles (SPIONs) due to a surface-immobilized lipid layer. Lipid coating was accomplished in different buffer systems, pH 7.4, using an equimolar mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and l-α-dipalmitoylphosphatidyl glycerol (DPPG). Particle size and zeta potential were measured by dynamic laser light scattering. Heating behavior within an alternating magnetic field was compared between the commercial MFG-1000 magnetic field generator at 7 mT (1 MHz) and an experimental, laboratory-made magnetic hyperthermia system at 16.6 mT (13.7 MHz). The results revealed that product quality of lipid-coated SPIONs was significantly dependent on the colloidal stability of uncoated SPIONs during the coating process. Greatest stability was achieved at 0.02 mg/mL in citrate buffer (mean diameter = 80.0 ± 1.7 nm; zeta potential = -47.1 ± 2.6 mV). Surface immobilization of an equimolar DPPC/DPPG layer effectively reduced the impact of buffer components on particle aggregation. Most stable suspensions of lipid-coated nanoparticles were obtained at 0.02 mg/mL in citrate buffer (mean diameter = 179.3 ± 13.9 nm; zeta potential = -19.1 ± 2.3 mV). The configuration of the magnetic field generator significantly affected the heating properties of fabricated SPIONs. Heating rates of uncoated nanoparticles were substantially dependent on buffer composition but less influenced by particle concentration. In contrast, thermal behavior of lipid-coated nanoparticles within an alternating magnetic field was less influenced by suspension vehicle but dramatically more sensitive to particle concentration. These results underline the advantages of lipid-coated SPIONs on colloidal stability without compromising magnetically induced hyperthermia properties. Since phospholipids are biocompatible, these unique lipid-coated Fe3O4 nanoparticles offer exciting opportunities as thermoresponsive drug delivery carriers for targeted, stimulus-induced therapeutic interventions.PACS7550Mw; 7575Cd; 8185Qr

A new long-acting liposomal topical antifungal formula: human clinical study.

Purpose: To study the clinical effect of a topical controlled-release ophthalmic fluconazole liposomal formulation on patients with Candida keratitis. Methods: Eleven eyes of 11 patients with Candida albicans corneal fungal infection (proved by cultures) were included in this study. All were treated with topical liposomal fluconazole (2 mg/mL) 3 times daily. The response to the treatment was divided into 3 categories: complete improvement, complete healing with scar formation at the end of 1 month; partial improvement, decrease in the ulcer size at the end of 1 month; and no improvement, includes extension of ulcer size and/or perforation that necessitates other approaches of management. The patients were examined daily over a 30-day period, and the results were recorded. Results: Eleven eyes with C. albicans as proved with laboratory cultures were included in this study (7 men and 4 women). Three of the patients included in this study had diabetes mellitus, and 2 patients had rheumatoid arthritis. Mean corneal ulcer diameter (mean of both horizontal and vertical diameters) was 5.5 mm (range, 3.5–6.5 mm). Mean duration of the ulcers at presentation was 7.6 days (range, 3–14 days). Eight patients improved after 1 month, whereas 1 patient had partial improvement and 2 patients did not improve and underwent amniotic membrane transplantation. One of the nonimproved patients progressed to perforation, and keratoplasty was performed. Mean decimal notation best-corrected visual acuity on presentation was 0.06, which was not improved at the end of the study. Conclusions: Therapy with topical liposomal fluconazole (2 mg/mL) carries a high success rate and fast effect in treating patients with C. albicans keratitis.

Microemulsion for ocular delivery: ocular irritancy test and in vivo studies of anti-inflammatory action

Microemulsions are promising drug delivery systems for ocular delivery of drugs, especially water insoluble drugs such as diclofenac in its acid undissociated form. Microemulsions are characterized with high surfactant content (> 10 % w/w) in order to lower the interfacial tension which facilitates dispersion process during the preparation of microemulsion and provides a flexible film around the droplets. However, there are a few researches that have studied the possible irritation effect of microemulsion on the eye. Therefore, evaluation of the ocular irritancy is an important requirement in the development of ocular delivery vehicles such as microemulsions. Draize test using rabbits was used for evaluation of the ocular irritation potential of the prepared microemulsions. The efficacy of the anti-inflammatory action of the formulation showing the least Draize score was then evaluated using 3 % croton oil in 2-ethoxyethanol to induce corneal inflammation in rabbits. Results showed that the tested formulations, M5 and M6, were non irritant (NI) where they showed a Draize score of 8 and 14 respectively. When M5 was studied for its anti-inflammatory action and compared with marketed eye drops, Epifenac, it showed a significantly shorter recovery time compared to Epifenac eye drops.

In Vivo performance of ophthalmic preparations of betamethasone and phenylephrine hydrochloride in the rabbit eye: Effect of polyvinyl alcohol.

The effect of different concentrations of polyvinyl alcohol 14000 and 72000 (PVA 14 and 72) on the activity of betamethasone and phenylephrine hydrochloride in the rabbit eye was investigated. The polymer of higher molecular weight exerts a more pronounced effect at relatively lower viscosities. Effects on the intraocular pressure are more responsive to changes in viscosity than those on pupillary response.

In vitro release study of betamethasone and phenylephrine hydrochloride from ophthalmic preparations

Abstract The in vitro release of betamethasone and phenylephrine hydrochloride from ophthalmic solutions and gels was investigated. Linearization of release data of either drug or their combination was attempted according to zero-order, first-order and diffusion kinetics. The data obtained are directly in favour of a first-order mechanism both for betamethasone and phenylephrine hydrochloride and they show that the mechanism of drug release from solutions containing viscolizers or from hydrogels is independent of the nature of the drug in terms of its water solubility or ionization. The type of polymer or the increase in viscosity of the ophthalmic preparation do not indicate the release mechanism to any significant extent. The release rate constants of phenylephrine hydrochloride are consistently higher than those of betamethasone. The preparation based on carbomer is the only exception to this. The release rate constant of the drug is highly dependent on the viscosity of the ophthalmic solution. Below the critical viscosity of 5 cp a considerable lowering of the release rate constant takes place. In ophthalmic gel the release rate constant of either drug shows a very low dependency on the basic viscosity of the gel.

Effect of different ointment bases on ocular disposition of ethylphenylephrine in rabbit eyes

Abstract The influence of vehicle composition on the ocular disposition of ethylphenylephrine, a mydriatic drug used for the treatment of wide-angle glaucoma, has been studied. The vehicles investigated consisted of a hydrocarbon base, an absorption base (10% lanolin in a paraffin base) and a water-soluble base (polyvinyl alcohol, PVA, 15% in water). The albino rabbit was chosen as the animal model. The disposition of the drug in conjunctiva, cornea, iris-ciliary body and aqueous humor of the rabbit was monitored at 1, 2 and 4 h post-installation using extraction technique. At the early time period (1 h post-administration) both oleaginous and water-soluble bases were judged to perform adequately in that they provided approximately the same drug concentrations in various ocular tissues at the aqueous vehicle. However, after 4 h, the oleaginous base provided the highest concentrations of drug in the conjunctiva. The water-soluble PVA formulation gave significantly lower levels in the conjunctiva and the cornea. At this same point, the absorption base containing lanolin produced the highest drug concentration in the cornea, iris-ciliary body and aqueous humor. Collectively, these data suggest that of the 3 bases studied, the oleaginous base and the absorption base show most promise as vehicles to extend the residence time of ethylphenylephrine in the eye. Obviously the final choice of vehicle will also be influenced by factors such as the physical and chemical stability of the drug in the formulation chosen and patient acceptance.