Intense efforts to develop alternative materials for gelatine as a drug-delivery system are progressing at a high rate. Some of the materials developed are hard capsules made from alginate, carrageenan, hypromellose and cellulose. However, there are still some disadvantages that must be minimised or eliminated for future use in drug-delivery systems. This review attempts to review the preparation and potential of seaweed-based, specifically carrageenan, hard capsules, summarise their properties and highlight their potential as an optional main component of hard capsules in a drug-delivery system. The characterisation methods reviewed were dimensional analysis, water and ash content, microbial activity, viscosity analysis, mechanical analysis, scanning electron microscopy, swelling degree analysis, gel permeation chromatography, Fourier-transform infrared spectroscopy and thermal analysis. The release kinetics of the capsule is highlighted as well. This review is expected to provide insights for new researchers developing innovative products from carrageenan-based hard capsules, which will support the development goals of the industry.

Topical Administration Effect of Sargassum duplicatum and Garcinia mangostana Extracts Combination on Open Wound Healing Process in Diabetic Mice: This research aimed to determine the topical administration effect of the combination of Sargassum duplicatum and Garcinia mangostana extracts to ameliorate diabetic open wound healing. The study used 24 adult males of Mus musculus (BALB/c strain, 34 months, 3040g). They were divided into normal control groups (KN) and diabetic groups. The diabetic group was streptozotocin-induced and divided further into three treatment groups: the diabetic control group (KD), the S. duplicatum treatment group (PA), and the combination of S. duplicatum and G. mangostana treatment group (PAM). The dose of treatment was 50mg/kg of body weight. Each group was divided into three treatment durations, which were 3 days, 7 days, and 14 days. The wound healing process was determined by wound width, the number of neutrophils, macrophages, fibroblasts, fibrocytes, and collagen density. Histological observation showed that the topical administration of combination extracts increased the re-epithelialization of the wounded area, fibroblasts, fibrocytes, and collagen synthesis. The topical administration of combination extracts also decreased the number of neutrophils and macrophages. This study concluded that the topical administration of the combination of S. duplicatum and G. mangostana extracts improved the open wound healing process in diabetic mice.

Diabetes mellitus is a group of metabolic disorders characterized by high blood-glucose levels over a prolonged period that causes complications when an open wound is present. Alginate is an antioxidant and a good absorbent of exudates. Okra fruit contains flavonoids that can act as antioxidants. The antioxidant properties of extracts combination reduce blood-glucose levels significantly to accelerate the activities of wound-healing processes on diabetic mice. Alginate was characterized by Size Exclusion Chromatography-Multiple Angle Laser Light Scattering (SEC-MALLS), thermal stability and Proton Nuclear Magnetic Resonance (¹H-NMR). The evaluation of wound healing on 36 male mice were divided into 12 groups including normal control (NC), diabetics control (DC), alginate (DA) and alginate–okra (DAO) groups in three different times by histopathology test on skin tissue. The results of SEC-MALLS analysis showed that alginate as single and homogeneous polysaccharide. The ¹H-NMR spectrum showed that the mannuronate/guluronate ratio of the used alginate was 0.91. Alginate, okra fruit extract and their combination were classified as moderate and strong antioxidants. The numbers of fibrocytes, fibroblasts, collagen densities had significantly increased from three to seven days. In contrast, wound width, neutrophil, macrophages had significantly decreased at 14 days. The administration of extracts combination increased the re-epithelization of the wound area and wound-healing process on diabetic mice.

The release of drugs from solid drug delivery materials has been studied intently in recent years. Quantitative analyses achieved from in vitro dissolution becomes easier if a zero-order mathematical model is used. Non-gelatin nutraceutical hard-shell capsules of zero size (approximately 0.7-0.8 cm) were produced from carrageenan-based natural polymers, namely carrageenan-alginate (CA) and carrageenan-starch (CS). Disintegration, dissolution and zero-order drug release kinetics of hard-shell capsules containing 100 mg of salicylamide were studied. The disintegration time of CA and CS were observed to be less than 30 min for both CA and CS. In vitro dissolution profile showed that the percentage dissolution of CA capsules was better at pH 4.5, while that of CS was poor at pH 1.2, 4.5 and 6.8. Determination of drug release kinetics profiles of carrageenan-based hardshell capsules utilized the Noyes-Whitney and Peppas-Sahlin modification rules for zero-order. The drug release from carrageenan-based capsules followed zero-order kinetics, especially at pH 6.8, and was compared to the Higuchi model. Salicylamide in CA hard-shell capsules at a pH 6.8 had a release rate constant (k_H) of 2.91 %(ppm/ ppm) min^-1/2, while the release rate constant of CS was 0.36 %(ppm/ppm) min^-1.

Hard-shell capsules commonly consist of gelatin which is not a universal material considering it is extracted from animal parts. Moreover, the mad cow disease triggered the scrutinization of the use of gelatin in pharmaceutical products. Hence, an alternative to conventional hard-shell capsules is needed. Carrageenan- (CRG-) based hard-shell capsules were successfully prepared by cross-linking CRG with maltodextrin (MD) and plasticizing with sorbitol (SOR). These CRG-MD/SOR hard-shell capsules were produced as an alternative to conventional hard-shell capsules in the oral drug delivery system (DDS). The physical properties of CRG-MD/SOR capsules were characterized using the degree of swelling, FTIR, and SEM analyses. The disintegration and dissolution profile release of paracetamol from CRG-MD/SOR hard-shell capsules was performed in an aqueous medium with three different pH levels. The degree of swelling of CRG-MD/SOR was 529.23±128.10%. The main peaks in the FTIR spectrum of CRG-MD/SOR were at 1248, 930, 847, and 805 cm⁻¹ for ester sulfate groups, 3,6-anhydrogalactose, galactose-4-sulfate, and 3,6-anhydrogalactose-2-sulfate, respectively. The SEM analysis exhibited minuscule pores on the surface of CRG and CRG-MD/SOR at 5000 times of magnification. The CRG-MD/SOR capsules required 18.47±0.11 min on average to disintegrate. The CRG-MD/SOR dissolution was better in a weakly acidic medium (pH 4.5) than in a strongly acidic (pH 1.2) and neutral (pH 6.8) media. Based on the aforementioned results, CRG-MD/SOR capsules are the potential candidate to replace conventional hard-shell capsules.

A diabetic foot ulcer is an open wound that can become sore and frequently occurs in diabetic patients. Alginate has the ability to form a hydrophilic gel when in contact with a wound surface in diabetic patients. Xanthones are the main compounds of mangosteen rind and have antibacterial and anti-inflammatory properties. The purpose of this research was to evaluate the wound healing and antioxidants assay with a combination of alginate from S. ilicifolium and mangosteen rind combination extracts on a diabetic mice model. The characterization of alginate was carried out by size exclusion chromatography with multiple angle laser light scattering (SEC-MALLS) and thermogravimetric analysis (TGA). The M/G ratio of alginate was calculated by using proton nuclear magnetic resonance (¹H NMR). The antioxidant activity of mangosteen rind and the combination extracts was determined using the DPPH method. The observed parameters were wound width, number of neutrophils, macrophages, fibrocytes, fibroblasts, and collagen densities. The 36 male mice were divided into 12 groups including non-diabetic control (NC), diabetes alginate (DA), alginate–mangosteen (DAM), and diabetes control (DC) groups in three different groups by a histopathology test on skin tissue. The treatment was carried out for 14 days and mice were evaluated on Days 3, 7, and 14. The SEC-MALLS results showed that the molecular weight and dispersity index (Ð) of alginate were 2.77 × 10⁴ Dalton and 1.73, respectively. The M/G ratio of alginate was 0.77 and described as single-stage decomposition based on TGA. Alginate, mangosteen rind extract, and their combination were divided into weak, medium, and strong antioxidant, respectively. The treatment of the DA and DAM groups showed a decrease in wound width and an increase in the number of fibrocytes, fibroblasts, and macrophages. The number of neutrophils decreased while the percentage of collagen densities increased for all the considered groups.