Development of Cinnarizine Microballoons by Sequential Optimization and In Vivo Imaging by Gamma Scintigraphy

Background: The drug cinnarizine is used in the treatment of vertigo and migraine. The main drawback is its very low water solubility which causes unpredictable bioavailability. Solubility is better in acidic pH. Therefore, gastro-retentive formulation would be beneficial to improve the bioavailability of the drug. Objective: The objective of the study was to prepare floating microballoons of cinnarizine which would float in the gastric fluid and release the drug in a sustained manner. Methods: Microballoons were prepared by diffusion solvent evaporation technique using polymers (Eudragit® S100, Eudragit® RLPO, Eudragit RL®100), characterised by FTIR, XRD, DSC and optimized by sequential simplex design. For optimization, formulations were graded with respect to formulation efficiency (percentages of yield, sphericity and drug content) and performance index (buoyancy and dissolution efficiency), from which the overall response of the formulations was determined. Finally, the optimized formulation was radiolabelled with 99mTc-MIBI and fed to Wistar albino rats and was evaluated for gastric retention by gamma scintigraphic study. Results: FTIR studies indicated drug and polymers were compatible. DSC and XRD analysis confirmed that the drug was in amorphous state in the formulation. SEM studies confirmed the sphericity of the microballoons. Formulation N7 showed the best overall response (65.61) which was the nearest to the target. Gamma scintigraphic study confirmed that the formulation was retained in the stomach for more than 5 h. Conclusion: The results indicated that floating microballoons of cinnarizine would stay in the stomach for prolonged period and thereby improve the bioavailability of the drug.

Gastroparesis in carcinoma gallbladder: a scintigraphic study

Background: Gastroparesis is characterized by delayed gastric emptying in the absence of mechanical gastric outlet obstruction. There is strong association of gastroparesis with carcinoma gallbladder. The aim of the study was to find out the incidence of delayed gastric emptying in carcinoma gallbladder and its correlation with symptoms of stasis and stage of the disease.Methods: Patients diagnosed with carcinoma gallbladder and their matched controls were included in this study. Patients with mechanical gastric outlet obstruction were excluded. All patients underwent contrast enhanced computer tomography scan and radio labeled (Technitium 99) solid meal Scintigraphy study. Normal gastric emptying time was calculated from control group as Mean +2SD.Results: 30 patients were matched with 20 controls after obtaining informed consent. Upper limit of gastric emptying time is 55.09 minutes. Adenocarcinoma was the commonest histological subtype (50%), abdominal pain was the commonest symptom (86.7%) and hepatomegaly was the commonest sign (46.7%), GETt1/2 for patients was 66.72±26.52 minutes while it was 40.53±7.28 minutes in controls (p <0.05). Gastroparesis increased with advancing stage of carcinoma gallbladder (p <0.05). Symptoms of gastric stasis were seen only in 15.6% of patients.Conclusions: Patients with carcinoma gallbladder can have gastroparesis without obvious symptoms of delayed gastric emptying. This delay in gastric emptying can be documented reliably using solid meal scintigraphic study even in patients without symptoms of gastroparesis. The pathophysiology of gastroparesis needs further study. It may be prudent to remember that while performing palliative bypass surgery for gastric outflow obstruction, that in patients with carcinoma gallbladder, the gastrojejunostomy may not function as expected due to delayed gastric emptying.