Amirali Ebrahimi

A novel formulation for solubility and content uniformity enhancement of poorly water-soluble drugs using highly-porous mannitol.

The present study investigates the enhancement of the dissolution rates for poorly-water soluble drugs by a new adsorption method. The results show that the current adsorption method enhanced the dissolution rate of both nifedipine and indomethacin to a significant extent by nano-confinement of drugs into the pore spaces of highly-porous excipients. Porous mannitol particles with a surface area and pore volume of 6.3 ± 0.1 m(2) g(-1) and 0.036 ± 0.002 ml g(-1), respectively, were drug loaded in two different concentrations of indomethacin and nifedipine. The results of drug loading for nifedipine showed an increase from 3.2 ± 0.1% w/w for a 0.08 M drug solution to 9.1 ± 0.3% w/w drug loading for a 0.16 M drug solution, while indomethacin had slightly better performance for the adsorption process, with 4.1 ± 0.2% w/w and 12.6 ± 0.4% w/w for 0.08 M and 0.16 M concentrations of indomethacin, respectively, in the final formulation. This result also indicated highly-uniform blends with a percentage relative standard deviation of less than 4% for drug-loaded mannitol in both nifedipine and indomethacin. This method gave a significant enhancement of the dissolution rate for both drugs due to nano-confinement of drugs into porous excipients and high solubility of porous mannitol, with 80% drug release within the first 15 min for the drug-loaded samples.

Incorporation of acetaminophen as an active pharmaceutical ingredient into porous lactose

A new formulation method for solid dosage forms with drug loadings from 0.65 ± 0.03% to 39 ± 1% (w/w) of acetaminophen (APAP) as a model drug has been presented. The proposed method involves the production of highly-porous lactose with a BET surface area of 20 ± 1 m(2)/g as an excipient using a templating method and the incorporation of drug into the porous structure by adsorption from a solution of the drug in ethanol. Drug deposition inside the carrier particles, rather than being physically distributed between them, eliminated the potential drug/carrier segregation, which resulted in excellent blend uniformities with relative standard deviations of less than 3.5% for all drug formulations. The results of DSC and XRD tests have shown deposition of nanocrystals of APAP inside the nanopores of lactose due the nanoconfinement phenomenon. FTIR spectroscopy has revealed no interaction between the adsorbed drug and the surface of lactose. The final loaded lactose particles had large BET surface areas and high porosities, which significantly increased the crushing strengths of the produced tablets. In vitro release studies in phosphate buffer (pH 5.8) have shown an acceptable delivery performance of 85% APAP release within 7 minutes for loaded powders filled in gelatin capsules.

Spray Drying and Crystallization of Lactose with Humid Air in a Straight-Through System

The effects of different humidities on process yields and degrees of crystallinity have been studied for spray-dried powders from the spray drying of lactose with humid air in a straight-through system. According to Williams-Landel-Ferry (WLF) kinetics, it was suggested that a higher particle temperature and lower glass transition temperature would increase the crystallization rates of the particles during the spray-drying process. Freshly humidified air produced by a Buchi-B290 spray dryer as a humidifier before the main spray dryer decreased the particle glass transition temperature (Tg), while allowing the particle temperature (Tp) to reach higher values by using an insulated drying chamber. The results showed that higher Tp − Tg, as a result of applying humid air, improved the process yield from 21 ± 4% to 26 ± 2% and the lactose crystallinity by decreasing the latent heat of crystallization for the powder products from 43 ± 1 J/g to 30 ± 11 J/g. It has been found in this study that the humidity of the inlet air should be adjusted in such a way as to not exceed relative and absolute humidities of 2.7–3% and 65–70 g/kg DA, respectively, at the outlet of the drying chamber, to give the most crystalline particles.

Improving the dissolution rate of hydrophobic drugs through encapsulation in porous lactose as a new biocompatible porous carrier

T he dissolution rates of indomethacin (IMC) and nifedipine (NIF) as poorly water-soluble model drugs have been significantly improved by encapsulating their molecules in the porous structure of engineered-particles of lactose as a new biocompatible porous carrier. The formulation method used in this study utilized a template-based spray-drying technique for in-situ production of porous lactose followed by two solvent-based drug-loading methods: (i) adsorption from organic solution, and (ii) incipient wetness impregnation to incorporate the drugs inside the porous lactose. In both cases, the results of DSC and XRD have revealed the deposition of nano-sized crystals of drugs inside the nanopores due to the nanoconfinement phenomenon. Greater extents of drug loadings have been achieved during the indomethacin adsorption due to the hydrogen-bonding interaction with the surface of lactose, as determined by FTIR spectroscopy. The in vitro release studies in simulated gastric fluid (SGF) have shown faster release rates for the impregnated particles compared with drug-loaded particles via the adsorption method.

Effect of spray-drying temperature on the formation of flower-like lactose for griseofulvin loading

ABSTRACT The effect of spray‐drying temperature has been studied for the first time on the formation of flower‐like lactose for drug loading in this work. The synthesis of the flower‐like lactose involves two steps, namely spray drying and ethanol washing. Four inlet temperatures (140 °C, 150 °C, 160 °C and 200 °C) have been used in the spray‐drying step. The effect of the spray‐drying temperature was significant on the formation of flower‐like lactose, in terms of crystallinity, porosity and drug loading capacity. Higher inlet temperatures are more likely to produce lactose in the &bgr; form. The engineered flower‐like lactose is highly porous, with pores of 1.4, 3.4 and 29.3 nm (diameter). Compared with other inlet temperatures, the flower‐like lactose dried at 150 °C has the lowest degree of crystallinity, the largest pore surface area (38 ± 4 m2/g) and pore volume (0.65 ± 0.09 cm3/g), and the highest griseofulvin loading capacity (16.2 ± 0.3%, w/w). A griseofulvin dissolution test has suggested that the flower‐like lactose can be used as a drug carrier to enhance drug solubility. Graphical abstract Figure. No Caption available.

Role of templating agents in the spray drying and postcrystallization of lactose for the production of highly porous powders

ABSTRACT In this work, we report a method using templating techniques in spray drying to fabricate porous lactose with flower-like shapes. Three templating agents, including boric acid, citric acid, and ascorbic acid, have been used and compared for the production of flower-like lactose. The role of templating agents has been found to be significant in spray drying and postcrystallization of lactose. After spray drying, the boric acid (with a smaller size) is more likely to diffuse to the core of spray-dried particles than the other two templating acids. The morphology, pore structure, and crystallinity of the flower-like lactose have been found to be related to the use of different templating agents. The Brunauer–Emmet–Teller surface areas of the flower-like lactose are 29, 24, and 25 m2/g, respectively, for boric acid, citric acid, and ascorbic acid, as the templating agents. From the Barrett–Joyner–Halenda analysis, the citric acid-templated flower-like lactose has more large pores (radius > 61.8 Å), while the boric acid-templated lactose has more pores with a size of 28.2 Å (radius) and the ascorbic acid-templated lactose has more pores with a size of 15.2 Å (radius).