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.

Background: Ischemic heart disorders and accumulation of lipids in blood vessels could contribute to angina pectoris. Therefore, the aim of this study was to formulate sublingual tablets containing a novel combination of Atorvastatin calcium (ATOR) and Trimetazidine HCl (TMZ) for efficient treatment of coronary heart disorders. Methods: The dissolution rate of water-insoluble ATOR was enhanced via complexation with sulfobutyl ether-b-cyclodextrin (SBE-b-CD) and addition of soluplus as a polymeric solubilizer excipient. The solubilized ATOR and TMZ were compressed into a sublingual tablets by direct compression technique and evaluated for their tableting characteristics. In addition, a new validated method based on High Performance Thin Layer Chromatography (HPTLC) was developed for simultaneous determination of both drugs in pure forms and sublingual tablets. Results: The developed HPTLC method showed LODs of 0.056 and 0.013 lg/band and LOQs of 0.17, 0.040 lg/band for TMZ and ATOR, respectively and proved to be linear, accurate, precise and robust. The optimum formulation containing mixture of superdisintegrants; Ac-Di-Sol and crospovidone (4.8% w/w, each) showed the shortest disintegration time (65 s) and enhanced release profiles of both drugs. Conclusions: The prepared sublingual tablets combining ATOR and TMZ will be a promising dosage form for coronary heart disease patients with an instant action and improved patient compliance.