Objective: The aim of this work was to enhance the bioavailability of poorly soluble, anti-emetic drug; domperidone (DMP) having a poor oral bioavailability (13-17%) due to extensive first pass metabolism. The goal of this study was achieved through solubilization of DMP using solid dispersion technology followed by incorporation of solid dispersions into sublingual tablets to bypass pre-systemic metabolism. Methods: Solid dispersions of DMP with Pluronic F-68 were prepared in different weight ratios by fusion method and they were evaluated for their in vitro dissolution rate to select the best ratio for final formulation. Then, solid dispersions were formulated into sublingual tablets in combination with various soluble excipients. Sublingual tablets were prepared by direct compression technique and evaluated for their physical properties, in vitro dissolution rate and kinetics of drug release. The best formulae were selected for in vivo studies in rabbits in comparison with marketed oral tablets; Motinorm®. Results: Solid dispersions of DMP with Pluronic F-68 in a weight ratio of 1:7 (w/w) showed the highest dissolution rate and were selected for sublingual tablets formulation. Sublingual tablets formulae S16 (containing Fructose and 10% w/w Ac-Di-Sol) and S20 (containing Fructose and 10% w/w Explotab) showed the best results and were selected for in vivo studies in rabbits. The selected formulae showed marked enhancement of DMP bioavailability compared with the commercial oral tablets; Motinorm®, with relative bioavailability values of 432.49±10.13% and 409.32±11.59 % for S16 and S20, respectively. Conclusion: The results confirmed that sublingual tablets were an effective tool for DMP delivery with marked enhancement of bioavailability.

The aim of this work was to improve the solubility and dissolution rate of poorly-soluble, weakly-basic, antiemetic drug; domperidone (DMP) using solid dispersion technique. Solubility studies of DMP with various hydrophilic carriers including sorbitol, mannitol, PEG 4000, PEG 6000, pluronic F-68 and pluronic F-127 were performed. Pluronic F-68 and pluronic F-127 showed the highest solubilizing effect on DMP and therefore; they were selected for the preparation of solid dispersions in different weight ratios by the fusion method. The solid dispersions were characterized using Fourier-transform infrared spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (P-XRD), solubility determination and in-vitro dissolution rate studies. FT-IR and DSC studies confirmed the absence of incompatibilities between DMP and the used carriers. DSC and P-XRD studies proved the transformation of drug from crystalline to amorphous state in the prepared solid dispersions. The results showed marked improvement of DMP solubility and dissolution rate from the solid dispersions compared with the pure drug and indicated the superiority of solid dispersions prepared with pluronic F-68 over those prepared with pluronic F-127. It can be concluded that solid dispersion technique was an effective tool in the enhancement of DMP dissolution.

The aim of this work was to improve the solubility and dissolution rate of poorly-soluble, weakly-basic, antiemetic drug; domperidone (DMP) using solid dispersion technique. Solubility studies of DMP with various hydrophilic carriers including sorbitol, mannitol, PEG 4000, PEG 6000, pluronic F-68 and pluronic F-127 were performed. Pluronic F-68 and pluronic F-127 showed the highest solubilizing effect on DMP and therefore; they were selected for the preparation of solid dispersions in different weight ratios by the fusion method. The solid dispersions were characterized using Fourier-transform infrared spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (P-XRD), solubility determination and in-vitro dissolution rate studies. FT-IR and DSC studies confirmed the absence of incompatibilities between DMP and the used carriers. DSC and P-XRD studies proved the transformation of drug from crystalline to amorphous state in the prepared solid dispersions. The results showed marked improvement of DMP solubility and dissolution rate from the solid dispersions compared with the pure drug and indicated the superiority of solid dispersions prepared with pluronic F-68 over those prepared with pluronic F-127. It can be concluded that solid dispersion technique was an effective tool in the enhancement of DMP dissolution.

The aim of this work was to improve the solubility and dissolution rate of poorly-soluble, weakly-basic, antiemetic drug; domperidone (DMP) using solid dispersion technique. Solubility studies of DMP with various hydrophilic carriers including sorbitol, mannitol, PEG 4000, PEG 6000, pluronic F-68 and pluronic F-127 were performed. Pluronic F-68 and pluronic F-127 showed the highest solubilizing effect on DMP and therefore; they were selected for the preparation of solid dispersions in different weight ratios by the fusion method. The solid dispersions were characterized using Fourier-transform infrared spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (P-XRD), solubility determination and in-vitro dissolution rate studies. FT-IR and DSC studies confirmed the absence of incompatibilities between DMP and the used carriers. DSC and P-XRD studies proved the transformation of drug from crystalline to amorphous state in the prepared solid dispersions. The results showed marked improvement of DMP solubility and dissolution rate from the solid dispersions compared with the pure drug and indicated the superiority of solid dispersions prepared with pluronic F-68 over those prepared with pluronic F-127. It can be concluded that solid dispersion technique was an effective tool in the enhancement of DMP dissolution.

The aim of this work was to improve the solubility and dissolution rate of poorly-soluble, weakly-basic, antiemetic drug; domperidone (DMP) using solid dispersion technique. Solubility studies of DMP with various hydrophilic carriers including sorbitol, mannitol, PEG 4000, PEG 6000, pluronic F-68 and pluronic F-127 were performed. Pluronic F-68 and pluronic F-127 showed the highest solubilizing effect on DMP and therefore; they were selected for the preparation of solid dispersions in different weight ratios by the fusion method. The solid dispersions were characterized using Fourier-transform infrared spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (P-XRD), solubility determination and in-vitro dissolution rate studies. FT-IR and DSC studies confirmed the absence of incompatibilities between DMP and the used carriers. DSC and P-XRD studies proved the transformation of drug from crystalline to amorphous state in the prepared solid dispersions. The results showed marked improvement of DMP solubility and dissolution rate from the solid dispersions compared with the pure drug and indicated the superiority of solid dispersions prepared with pluronic F-68 over those prepared with pluronic F-127. It can be concluded that solid dispersion technique was an effective tool in the enhancement of DMP dissolution.

Solubility is a significant physicochemical parameter that affects the absorption, bioavailability and therapeutic effectiveness of any drug. Formulation development would fail if drug has a poor aqueous solubility. The low aqueous solubility of drug substances will lead to inadequate absorption and consequently, low bioavailability. Improvement of the aqueous solubility and dissolution rate of hydrophobic drugs remains one of the most difficult challenges in drug development process. Among various techniques used to improve poor aqueous solubility of drugs, solid dispersion technology has been extensively used in the literature and has become one of the well-established pharmaceutical procedures during formulation process. Although the technique seems to be “a part of the past”, literature tells us that it is still used and developed to suit current needs of pharmaceutical industry. This review article highlights recent advances in solid dispersion technology and its applications in contemporary pharmaceutical research.

In an attempt to decrease the dose, anticipated side effects, and the cost of production of glibenclamide, GLC, a potent oral hypoglycemic drug, the enhancement of the dissolution and hence the oral bioavailability were investigated. Adsorption and co-adsorption techniques using carriers having a very large surface area and surface active agents were utilized to enhance the drug dissolution. Moreover, the Langmuir adsorption isotherms were constructed to identify the type and mechanism of adsorption. The optimized formulation showing the highest in vitro release was compressed into mini-tablet to facilitate drug administration to elderly patients and those having swallowing difficulties. The produced mini-tablets were tested for their mechanical strength and in vitro release pattern. In addition, the pharmacodynamic and pharmacokinetic studies in New Zealand rabbits were performed using the optimized mini-tablet formulation. Mini-tablets containing GLC co-adsorbate with Pluronic F-68 and Laponite RD showed 100 ± 1.88% of GLC released after 20 min. Pharmacodynamic studies in rabbits revealed significantly higher (p ≤ 0.05) hypoglycemic effect with the optimized mini-tablets at a lower GLC dose compared to mini-tablets containing the commercial GLC dose. Moreover, pharmacokinetic analysis showed significantly higher (p ≤ 0.05) AUC, Cmax, and shorter Tmax. The optimized mini-tablet formulation showed 1.5-fold enhancement of the oral bioavailability compared to mini-tablets containing untreated GLC. It could be concluded that the co-adsorption technique successfully enhanced the oral bioavailability of GLC. Furthermore, the produced mini-tablets have a higher oral bioavailability with a lower GLC dose, which could offer economic benefit for industry as well as acceptability for patients.

In an attempt to decrease the dose, anticipated side effects, and the cost of production of glibenclamide, GLC, a potent oral hypoglycemic drug, the enhancement of the dissolution and hence the oral bioavailability were investigated. Adsorption and co-adsorption techniques using carriers having a very large surface area and surface active agents were utilized to enhance the drug dissolution. Moreover, the Langmuir adsorption isotherms were constructed to identify the type and mechanism of adsorption. The optimized formulation showing the highest in vitro release was compressed into mini-tablet to facilitate drug administration to elderly patients and those having swallowing difficulties. The produced mini-tablets were tested for their mechanical strength and in vitro release pattern. In addition, the pharmacodynamic and pharmacokinetic studies in New Zealand rabbits were performed using the optimized mini-tablet formulation. Mini-tablets containing GLC co-adsorbate with Pluronic F-68 and Laponite RD showed 100 ± 1.88% of GLC released after 20 min. Pharmacodynamic studies in rabbits revealed significantly higher (p ≤ 0.05) hypoglycemic effect with the optimized mini-tablets at a lower GLC dose compared to mini-tablets containing the commercial GLC dose. Moreover, pharmacokinetic analysis showed significantly higher (p ≤ 0.05) AUC, Cmax, and shorter Tmax. The optimized mini-tablet formulation showed 1.5-fold enhancement of the oral bioavailability compared to mini-tablets containing untreated GLC. It could be concluded that the co-adsorption technique successfully enhanced the oral bioavailability of GLC. Furthermore, the produced mini-tablets have a higher oral bioavailability with a lower GLC dose, which could offer economic benefit for industry as well as acceptability for patients.

Hepatocellular carcinoma (HCC), a common deadly malignancy, requires novel therapeutic strategies to improve the survival rate. Combining chemotherapy and gene therapy is a promising approach for increasing efficiency and reducing side effects. We report on the design of highly specific lipid nanoparticles (LNPs) encapsulating both the chemotherapeutic drug, sorafenib (SOR), and siRNA against the midkine gene (MK), thereby conferring a novel highly efficient anticancer effect on HCC. The LNPs were modified with a targeting peptide, SP94, which is selective for hepatic cancer cells (HCCs), thus permitting the specific delivery of the payload. MK-siRNA increased the sensitivity of HCCs, HepG2, to SOR (IC50 for SOR+MK-siRNA: 5 ± 1.50 μM compared to 9 ± 2.20 and 17 ± 2.60 μM for SOR+control siRNA and MK-siRNA, respectively). The selectivity was confirmed by cellular uptake, cytotoxicity, and gene-silencing studies in HCCs, HepG2, and Hepa 1–6, compared to other cancerous cells, HeLa, and normal cells, FL83B. The use of a novel pH-sensitive lipid, YSK05, increased the cytotoxic and gene knockdown efficiencies and limited extracellular drug release. The nanoparticles were also compatible with serum and showed no aggregation after long storage. The efficient and specific codelivery system reported here is a highly promising strategy for the treatment of HCC.

Hepatocellular carcinoma (HCC), a common deadly malignancy, requires novel therapeutic strategies to improve the survival rate. Combining chemotherapy and gene therapy is a promising approach for increasing efficiency and reducing side effects. We report on the design of highly specific lipid nanoparticles (LNPs) encapsulating both the chemotherapeutic drug, sorafenib (SOR), and siRNA against the midkine gene (MK), thereby conferring a novel highly efficient anticancer effect on HCC. The LNPs were modified with a targeting peptide, SP94, which is selective for hepatic cancer cells (HCCs), thus permitting the specific delivery of the payload. MK-siRNA increased the sensitivity of HCCs, HepG2, to SOR (IC50 for SOR+MK-siRNA: 5 ± 1.50 μM compared to 9 ± 2.20 and 17 ± 2.60 μM for SOR+control siRNA and MK-siRNA, respectively). The selectivity was confirmed by cellular uptake, cytotoxicity, and gene-silencing studies in HCCs, HepG2, and Hepa 1–6, compared to other cancerous cells, HeLa, and normal cells, FL83B. The use of a novel pH-sensitive lipid, YSK05, increased the cytotoxic and gene knockdown efficiencies and limited extracellular drug release. The nanoparticles were also compatible with serum and showed no aggregation after long storage. The efficient and specific codelivery system reported here is a highly promising strategy for the treatment of HCC.