Quinine hydrochloride (QHCl) has remained a very relevant antimalarial drug 400 years after its effectiveness was discovered. Unlike other antimalarials, the development of resistance to quinine has been slow. Hence, this drug is to date still used for the treatment of severe and cerebral malaria, for malaria treatment in all trimesters of pregnancy, and in combination with doxycycline against multidrug-resistant malaria parasites. The decline in its administration over the years is mainly associated with poor tolerability due to its gastrointestinal (GIT) side effects such as cinchonism, complex dosing regimen and bitter taste, all of which result in poor compliance. Hence, our research was aimed at redesigning quinine using nanotechnology and investigating an alternative route for its administration for the treatment of malaria. QHCl nanosuspension (QHCl-NS) for intranasal administration was prepared using lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising Phospholipon^® 90H and lipids (Softisan^® 154 or Compritol^®) in a 1:2 ratio, while Poloxamer^® 188 (P188) and Tween^® 80 (T80) were used as a stabilizer and a surfactant, respectively. The QHCl-NS formulated were in the nanosize range (68.60 ± 0.86 to 300.80 ± 10.11 nm), and highly stable during storage, though zeta potential was low (≤6.95 ± 0.416). QHCl-NS achieved above 80% in vitro drug release in 6 h. Ex vivo permeation studies revealed that formulating QHCl as NS resulted in a 5-fold and 56-fold increase in the flux and permeation coefficient, respectively, thereby enhancing permeation through pig nasal mucosa better than plain drug solutions. This implies that the rate of absorption as well as ease of drug permeation through porcine nasal mucosa was impressively enhanced by formulating QHCl as NS. Most importantly, reduction in parasitaemia in mice infected with Plasmodium berghei ANKA by QHCl-NS administered through the intranasal route (51.16%) was comparable to oral administration (52.12%). Therefore, redesigning QHCl as NS for intranasal administration has great potential to serve as a more tolerable option for the treatment of malaria in endemic areas.

Surface modified self-nanoemulsifying formulations (SNEFs) loaded with gentamicin were formulated using suitable blends of soybean oil, a mixture of Kolliphor ^® P188 and Kolliphor ^® EL as surfactants, and Transcutol ^® HP as co-surfactant, and administered orally to white albino rats for evaluation of anti-pneumococcal activity against Streptococcus pneumoniae . Droplet size and zeta potential measurements showed that SNEFs had mean droplet sizes in the range of 80.7±0.5–210.2±0.0, and were stable with mean zeta potential in the range of –25.2±3.0 to –42.5±1.3 mV. Preliminary screening against S. pneumoniae in vitro revealed that gentamicin-loaded SNEFs had better bacterial inhibition than the standard drug, and at a low minimum inhibitory concentration (MIC) of 2.5 mg/mL. Gentamicin delivered into cerebrospinal fluid of rats from orally administered SNEFs produced a prolonged and enhanced activity against S. pneumoniae at a dose of 7 mg/kg than the standard drug at the same dose. Hence, results from this study showed that the activity of gentamicin against S. pneumoniae was improved by formulation as surface modified SNEFs.

Aim: The aim of this study is to formulate and evaluate solid dispersions of indomethacin based on Gelucire 50/13, Hydroxylpropyl methylcellulose and/or Hydroxylpropyl cellulose hybrid binary or ternary system, with a view of enhancing oral bioavailability, sustaining drug release with optimum anti-inflammatory activity and minimal side effects. Methodology: Solid dispersions were prepared by solvent-evaporation method at varying polymer ratios (with HPMC and Gelucire 50/13 at 1:1, 2:1, 3:1, 4:1, 1:2, 1:3, 1:4 and HPMC, HPC and Gelucire 50/13 at 1:1:1) with a constant concentration of indomethacin (100 mg). The formulations were characterized in terms of morphology, stability and drug content. The release profiles of indomethacin from the solid dispersions were examined in vitro using two different media i.e. SGF and SIF, without enzymes. The anti-inflammatory properties were evaluated. Results: The formulated solid dispersions were stable and almost spherical to irregularly-shaped. The drug content of the formulations was accepted according to the Pharmacopoeial limit. In vitro dissolution studies showed an increased dissolution rate at pH 7.4 compared to pH 1.2 for the various batches with solid dispersions showing a faster and sustained dissolution rate than the pure crystalline drug. The percentage inhibitions of edema produced by the formulations in the in vivo studies were significantly higher and sustained than the pure drug. Conclusion: Solid dispersions prepared with these biodegradable polymer hybrids, HPMC/HPC/Gelucire^® 50/13, showed promising potential in clinical practice for enhancing the delivery of indomethacin.