viscosity | Acta Medica Marisiensis

Design, development and optimization of gastro-retentive floating in-situ gels loaded with carvedilol microspheres using response surface methodology

Latha Kukati¹, Aisha Rahman¹, Aymen Fatima¹, Vyshak R Menon¹, Lakshmi SVVNSM²

1. G. Pulla Reddy College of Pharmacy, Osmania University, Hyderabad, Telangana, India
2. Department of pharmacognosy, Vishnu Institute of Pharmaceutical Education and Research, Narsapur, Medak, Telangana, India

DOI: 10.2478/amma-2025-0011

Aim: The goal of this study was to formulate and optimize gastro-retentive floating in-situ gel comprising optimized microspheres by Box-Behnken design.
Methods: Gellan gum, k-carrageenan were used as gelling polymers and calcium carbonate as complexing and gas generating agent. For optimization X1 (concentration of k-carrageenan), X2 (concentration of calcium carbonate) and X3 (concentration of tri sodium citrate) were considered as factors and Y1 (viscosity), Y2 (floating lag time), Y3 (drug release at 8 hrs) as responses. 17 formulations obtained from the design were prepared and evaluated for various parameters.
Results and discussion: The optimized floating in-situ gel formulation obtained from the design was milky white liquid with viscosity of 355.13 cP, showed buoyancy lag time of 104 seconds and remained buoyant for >24 hrs. 27.49 % drug was released from the in-situ gel at 8 hrs indicating controlled drug release. From the stability studies which were conducted for 4 weeks, it was determined that the optimized floating in-situ gel formulation was stable.
Conclusion: This study highlights the potential utilization of microspheres in the gastro-retentive floating in-situ gel.

Rheological Behavior of Sodium Valproate Suppositories

Tăurean Alexandrina¹, Ciurba Adriana², Todoran Nicoleta², Bumb Doina³, Cazacincu R.⁴

1 Clinical County Hospital Mureş, Pharmacy number 3, Tg. Mureş, Romania
2 Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Medicine and Pharmacy Tg. Mureş, Romania
3 Regional Center of Public Health, Tg. Mureş, Romania
4 Department of Pharmaceutical Industry, Faculty of Pharmacy, University of Medicine and Pharmacy “Ovidius”, Constanţa, Romania

Background: Because the valproic derivates are frequently used in the treatment of epilepsy, bipolar disorders, major depression cases, migraines and other neurological disorders at children, the rectal administration is a real advantage.
Aim: In this study we aimed to assess the influence of the formulation on the rheological characteristics of lipophilic suppository bases Suppocire NAI, Witepsol W35, Massa Estarinum299, Lipex403, containing Cetyl alcohol and Solutol HS15, respectively.
Methods: Spreadability was determined by the Pozo Ojeda-Sune Arbussa method. Half a gram suppository was placed on the bottom plaque of the extensiometer, and the upper plaque was added over it. After equal intervals of time (1 minute) different weights (2, 5, 10, 20, 30, 40, 50, 100, 150, 200, 250, 300, 350, 400, 500 g) were placed. Following each weight addition, the diameters of the obtained circles were measured, and the corresponding area was calculated. The viscosity was determined using the Brookfield (DV-II +Pro) rotational viscosimeter. The measurements were performed at 37±0.5°C and 5, 10, 20, 50, 100, 50, 20, 10, 5 rpm.
Results: The experimental results demonstrated that sodium valproate as active substance induces an increase in viscosity and consequently a decrease in the spreading capacity of the lipophilic suppository bases used. Lipex403 (a base consisting in fatty acids) manifests the lowest viscosity compared to the bases consisting in mixtures of glycerides (Suppocire NAI, Witepsol W35, Massa Estarinum 299). Solutol HS15 as emulsifier determines a higher decrease in viscosities and a better spreading capacity than Cetyl alcohol. Sodium valproate suppositories obtained with Lipex403 as excipient base show plastic flow characteristics without thixotropy.
Conclusions: The experimental results demonstrated that sodium valproate as active substance induces an increase in viscosity and consequently a decrease in the spreading capacity of the lipophilic suppository bases used. Solutol HS15 determines a higher decrease in viscosities and a better spreading capacity than Cetyl alcohol.