Insulin-loaded alginic acid nanoparticles for sublingual delivery.

Alginic acid nanoparticles (NPs) containing insulin, with nicotinamide as permeation enhancer were developed for sublingual delivery. The lower concentration of proteolytic enzymes, lower thickness and enhanced retention due to bioadhesive property, were relied on for enhanced insulin absorption. Insulin-loaded NPs were prepared by mild and aqueous based nanoprecipitation process. NPs were negatively charged and had a mean size of ∼200 nm with low dispersity index. Insulin loading capacities of >95% suggested a high association of insulin with alginic acid. Fourier Transform Infra-Red Spectroscopy (FTIR) spectra and DSC (Differential Scanning Calorimetry) thermogram of insulin-loaded NPs revealed the association of insulin with alginic acid. Circular dichroism (CD) spectra confirmed conformational stability, while HPLC analysis confirmed chemical stability of insulin in the NPs. Sublingually delivered NPs with nicotinamide exhibited high pharmacological availability (>100%) and bioavailability (>80%) at a dose of 5 IU/kg. The high absolute pharmacological availability of 20.2% and bioavailability of 24.1% in comparison with subcutaneous injection at 1 IU/kg, in the streptozotocin-induced diabetic rat model, suggest the insulin-loaded alginic acid NPs as a promising sublingual delivery system of insulin.

Enhanced insulin absorption from sublingual microemulsions: effect of permeation enhancers.

Microemulsions of insulin (50 IU/mL) comprising permeation enhancers were formulated for sublingual delivery. Circular dichroism (CD) spectra indicated conformational stability, while chemical stability was confirmed by high-performance liquid chromatography (HPLC). CD spectra of insulin in combination with permeation enhancers revealed attenuation of molar ellipticity at 274 nm in the order TCTP > TC-AOT > TC > TC-NMT > Sol P > insulin solution. The molar ellipticity ratios at 208/222 nm confirmed dissociation of insulin in the microemulsions with the same rank order. Matrix-assisted laser diffraction ionization mass spectra (MALDI) revealed a significant shift in intensity signals towards monomer and dimers with a substantially high ratio of monomers, especially in the presence of the TCTP and TC-AOT. Permeation through porcine sublingual mucosa correlated with the dissociation data. A high correlation between the ratio of molar ellipticity at 208/222 nm and serum glucose levels (r (2) > 0.958) and serum insulin levels (r (2) > 0.952) strongly suggests the role of dissociation of insulin on enhanced absorption. While all microemulsions revealed a reduction in serum glucose levels and increase in serum insulin levels, significant differences were observed with the TCTP and TC-AOT microemulsions. High pharmacological availability >60 % and bioavailability >55 % compared to subcutaneous insulin at a low dose of 2 IU/kg appears highly promising. The data clearly suggests the additional role of the permeation enhancers on dissociation of insulin on enhanced sublingual absorption from the microemulsions.

Novel ion exchange resin-based combination drug-delivery system for treatment of gastro esophageal reflux diseases

The present study involves preparation and characterization of a combination tablet of ranitidine in immediate release form and domperidone in sustained release form, using ion exchange resins. Ranitidine lowers acid secretion, while domperidone release over a prolonged period improves gastric motility thus justifying this combination in gastro esophageal reflux diseases (GERD) and ensuring patient compliance. Drug loading was carried out by batch method & resinates were characterized using FTIR, XRPD. Resinates were formulated as a combination tablet and evaluated for tablet properties & in vitro drug release. Resinates provided sustained release of domperidone and immediate release of ranitidine. IR and X-ray studies indicate complexation of drug and resin along with monomolecular distribution of drugs in amorphous form in the resin matrix. The tablets of resinate combination showed good tablet properties. In-vitro drug release gave desired release profiles and ex-vivo drug absorption studies carried out by placing everted rat intestine in dissolution medium indicated statistically significant similarity in absorption from test and marketed formulation. The novelty of this study is that the retardation in release of domperidone from resinates is achieved by presence of weak resin in the formulation.

O presente estudo envolve a preparação e a caracterização de associação do comprimido de ranitidina de liberação imediata e domperidona de liberação prolongada, utilizando resinas de troca iônica. A ranitidina diminui a secreção ácida, enquanto a liberação prolongada de domperidona melhora a motilidade gástica, justificando, dessa forma, a associação em doenças de refluxo gastroesofágico (DRGE) e garantindo a adesão do paciente. A carga de fármaco foi efetuada pelo método em batelada e os resinatos, caracterizados utilizando-se FTIR e XRPD. Os resinatos foram formulados como comprimido da associação e avaliados com relação às propriedades dos comprimidos e liberação do fármaco in vitro. Os resinatos proporcionaram a liberação prolongada da domperidona e a liberação imediata da ranitidina. IV e estudos de difração de raios X indicaram a complexação do fármaco e da resina junto com a distribuição monomolecular dos fármacos, em estado amorfo, na matriz da resina. Os comprimidos da associação do resinato apresentaram boas propriedades. Obtiveram-se os perfis de liberação in vitro e os estudos de absorção dos fármacos ex vivo realizados com intestino de rato em meio de dissolução indicaram semelhança significativa na absorção entre as formulações teste e comercializada. A inovação do trabalho é que o retardamento da liberação da domperidona dos resinatos é atingido pela presença de resina fraca na formulação.

Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery.

The purpose of this study was to prepare miconazole nitrate (MN) loaded solid lipid nanoparticles (MN-SLN) effective for topical delivery of miconazole nitrate. Compritol 888 ATO as lipid, propylene glycol (PG) to increase drug solubility in lipid, tween 80, and glyceryl monostearate were used as the surfactants to stabilize SLN dispersion in the SLN preparation using hot homogenization method. SLN dispersions exhibited average size between 244 and 766 nm. All the dispersions had high entrapment efficiency ranging from 80% to 100%. The MN-SLN dispersion which showed good stability for a period of 1 month was selected. This MN-SLN was characterized for particle size, entrapment efficiency, and X-ray diffraction. The penetration of miconazole nitrate from the gel formulated using selected MN-SLN dispersion as into cadaver skins was evaluated ex-vivo using franz diffusion cell. The results of differential scanning calorimetry (DSC) showed that MN was dispersed in SLN in an amorphous state. The MN-SLN formulations could significantly increase the accumulative uptake of MN in skin over the marketed gel and showed a significantly enhanced skin targeting effect. These results indicate that the studied MN-SLN formulation with skin targeting may be a promising carrier for topical delivery of miconazole nitrate.