Abstract:The solubility enhancement of diazepam and nitrazepam in water was analyzed depending on temperature and amount of α-cyclodextrin (α-CD), β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD). The interactions of drug-cyclodextrin in solution were investigated by the phase-solubility analysis. Diazepam (nitrazepam) content in aqueous complexation medium was analyzed UV spectrophotometrically. Classical solubility data were used to derive apparent stability constants (K 1:1 ) which were used to d… Show more
“…The phase solubility diagram of Pc-INH (as illustrated in Fig. 2 for γ -CD) showed B-type curves for all the CDs investigated, which suggests formation of poorly soluble complexes 48,49 . The aqueous solubility of Pc-INH at 25 °C (0.0016%) increased 4-, 8- and 11-fold with increasing amounts of α- CD (0–14%), β- CD (0–1.8%) and γ -CD (0–22%), respectively.…”
Section: Resultsmentioning
confidence: 94%
“…Although the K st values obtained were below the optimal values, 100–1000 M −1 , these data indicate the highest stability of γ -CD complexes. While complexation efficiency ( CE ) values for α- CD and β- CD were about 0.0007 and 0.0003, respectively, γ -CD’s CE was found to be 0.001, meaning at least one Pc-INH molecule is likely complexed by one in every 1000 molecules of γ -CD 48 . No significant differences were observed between the two experimental temperatures used.Figure 2Phase solubility diagrams for γ -CD inclusion complexes with Pc-INH.…”
Liposomes are reputed colloidal vehicles that hold the promise for targeted delivery of anti-tubercular drugs (ATBDs) to alveolar macrophages that host Mycobacterium tuberculosis. However, the costly status of liposome technology, particularly due to the use of special manufacture equipment and expensive lipid materials, may preclude wider developments of therapeutic liposomes. In this study, we report efficient encapsulation of a complex system, consisting of isoniazid-hydrazone-phthalocyanine conjugate (Pc-INH) in gamma-cyclodextrin (
γ
-CD), in liposomes using crude soybean lecithin by means of a simple organic solvent-free method, heating method (HM). Inclusion complexation was performed in solution and solid-state, and evaluated using UV-Vis, magnetic circular dichroism,
1
H NMR, diffusion ordered spectroscopy and FT-IR. The HM-liposomes afforded good encapsulation efficiency (71%) for such a large Pc-INH/
γ
-CD complex (PCD) system. The stability and properties of the PCD-HM-liposomes look encouraging; with particle size 240 nm and Zeta potential −57 mV that remained unchanged upon storage at 4 °C for 5 weeks. The release study performed in different pH media revealed controlled release profiles that went up to 100% at pH 4.4, from about 40% at pH 7.4. This makes PCD-liposomes a promising system for site-specific ATBD delivery, and a good example of simple liposomal encapsulation of large hydrophobic compounds.
“…The phase solubility diagram of Pc-INH (as illustrated in Fig. 2 for γ -CD) showed B-type curves for all the CDs investigated, which suggests formation of poorly soluble complexes 48,49 . The aqueous solubility of Pc-INH at 25 °C (0.0016%) increased 4-, 8- and 11-fold with increasing amounts of α- CD (0–14%), β- CD (0–1.8%) and γ -CD (0–22%), respectively.…”
Section: Resultsmentioning
confidence: 94%
“…Although the K st values obtained were below the optimal values, 100–1000 M −1 , these data indicate the highest stability of γ -CD complexes. While complexation efficiency ( CE ) values for α- CD and β- CD were about 0.0007 and 0.0003, respectively, γ -CD’s CE was found to be 0.001, meaning at least one Pc-INH molecule is likely complexed by one in every 1000 molecules of γ -CD 48 . No significant differences were observed between the two experimental temperatures used.Figure 2Phase solubility diagrams for γ -CD inclusion complexes with Pc-INH.…”
Liposomes are reputed colloidal vehicles that hold the promise for targeted delivery of anti-tubercular drugs (ATBDs) to alveolar macrophages that host Mycobacterium tuberculosis. However, the costly status of liposome technology, particularly due to the use of special manufacture equipment and expensive lipid materials, may preclude wider developments of therapeutic liposomes. In this study, we report efficient encapsulation of a complex system, consisting of isoniazid-hydrazone-phthalocyanine conjugate (Pc-INH) in gamma-cyclodextrin (
γ
-CD), in liposomes using crude soybean lecithin by means of a simple organic solvent-free method, heating method (HM). Inclusion complexation was performed in solution and solid-state, and evaluated using UV-Vis, magnetic circular dichroism,
1
H NMR, diffusion ordered spectroscopy and FT-IR. The HM-liposomes afforded good encapsulation efficiency (71%) for such a large Pc-INH/
γ
-CD complex (PCD) system. The stability and properties of the PCD-HM-liposomes look encouraging; with particle size 240 nm and Zeta potential −57 mV that remained unchanged upon storage at 4 °C for 5 weeks. The release study performed in different pH media revealed controlled release profiles that went up to 100% at pH 4.4, from about 40% at pH 7.4. This makes PCD-liposomes a promising system for site-specific ATBD delivery, and a good example of simple liposomal encapsulation of large hydrophobic compounds.
“…The ΔG values give insight on the dissolution conditions that favor the guest molecule solubilization where negative values indicate favorable conditions. 48 The ΔG calculated for the inclusion complexes 1 and 2 were negative indicating that IMQ interaction with βCD was spontaneous while the values obtained for the inclusion complexes 3 and 4 were positive. The results showed that the negative ΔG values and the stability of the inclusion complexes 1 and 2 were determined by the enthalpy contribution and, therefore, the complexation process was enthalpy-driven whereas the formation of inclusion complexes 3 and 4 was an entropy-driven process.…”
Imiquimod (IMQ), an immune response modifier, is used for topical treatment of basal cell carcinoma and actinic keratosis. The very poor aqueous solubility of imiquimod gives rise to difficulties in designing aqueous formulations with this drug. One approach that is widely used to enhance drug solubility is complexation with cyclodextrins. The formation of the inclusion complex between IMQ and β-cyclodextrin was investigated in solution and in solid state. IMQ aqueous solubility was improved in the presence of citric acid. The experimental results and molecular modeling indicated the formation of the inclusion complex in aqueous solution of citric acid pH 3.0; however, the low apparent stability constant suggested weak interaction between β-cyclodextrin and IMQ which hampered the use of this approach to improve imiquimod aqueous solubility and the development of an aqueous formulation containing IMQ in the same concentration as in the commercial product.
“…Generally, it is observed that poorly soluble drugs show non-linear trend in the phase solubility diagram. Complexation efficiency is regarded as a more accurate method for determination of the solubilizing efficiency of CDs because it is independent of both the intrinsic solubility of the drug and the intercept of phase solubility diagram 27 . The complexation efficiency of CLZ-HP-β-CD complex was found to be 3.61 x 10 -3 .…”
Section: Characterization Of Inclusion Complex: Phase Solubility Studmentioning
Low solubility and biovariability associated with cilostazol (CLZ) pose serious formulation problems despite several advancements in dosage form design. The present research work amalgamates two different solubility enhancement techniques, viz. spray drying and cyclodextrin inclusion complexation to produce amorphous composites of CLZ with increased solubility and dissolution characteristics. FTIR studies unveiled inclusion/ interaction of cyclohexane ring and tetrazole moiety of CLZ in the hydroxypropyl-beta-cyclodextrin (HP-β-CD) cavity. Thermal analysis by DSC showed a decrease in melting points of CLZ and HP-β-CD, indicating favorable complex formation. P-XRD studies revealed reduction in crystallinity and amorphization of CLZ in the complex. SEM indicated a drastic change in surface morphology compared to pure CLZ. These complexes were compressed into oral disintegrating tablets (ODTs) using direct compression technique. The ODTs were characterized for disintegration time, wetting time and in vitro dissolution. Remarkable improvement in solubility and in vitro dissolution characteristics was observed for ODTs in water and compendial dissolution media. Inclusion complexation with HP-β-CD, amorphous composites produced by spray drying technique and the use of multi-functional co-processed excipients like Pearlitol SD-200, Kollidon CL and MCC-200 are responsible for increased solubility and dissolution of CLZ INTRODUCTION: Cilostazol is a phosphodiesterase III inhibitor with therapeutic focus on cAMP. It exerts its vasodilatory action by inhibiting platelet aggregation induced by collagen, 5'-adenosine diphosphate (ADP), epinephrine, and arachidonic acid 1, 2. CLZ is primarily used in the treatment of intermittent claudication (IC) which is the primary symptom of peripheral arterial disease (PAD). Around 12 million people in USA alone have PAD, and as the world population is aging, the incidence is expected to rise 3. The best medical therapy for IC has only four drugs on its panel, amongst which CLZ has been approved by the US FDA 4, 5 .
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