منبع پایان نامه درباره interest، tradition، ACT
Figure 4.12: Newtonian behavior of κ-carrageenan in the concentration range of 0.25% to 1% at 50 °C 96
Figure 4.13: Flow curves of the mixture HHSS12-κC0.5 (•), 20%HHSS12 and 0.5% κ-carrageenan, κC0, 5 (×), and starch dispersions HHSS12 20% (□), 23% (○) and 25% (Δ). The temperature was 50 °C 97
Figure 4. 14: Flow curve of the HHSS12-κC0.5. Shear rate up 0 to 100 s-1 empty symbols, and down 100 to 0 s-1 filled symbols 98
Figure 4.15: Flow curves of mixtures of 25% starch HHSS12 with κ-carrageenan at different concentrations. Measurements were taken at 50 °C 99
Figure 4.16: Flow curves for 0.5% κ-carrageenan and mixtures of 25% dually modified cassava starches/κC0.5. Measurement temperature was 50 °C. 100
Figure 4.17: Mechanical spectrum of κC0.5 (solid lines ■, □), HHSS12 (solid lines ●, ○), and the mixture κC0.5-HHSS12 (■, □). Concentration of HHSS12 alone was 25% and in combination total concentration was 25%. G’: filled symbols, G”: empty symbols. Measurement temperature: 50 ° C. Strain amplitude: 1% 101
Figure 4.18: Variation of viscoelastic modulus G’ and G” as a function of temperature for κC0.5 and for the mixture of κC0.5 and HHSS12. a) Cooling from 50 °C to 20 °C. b) Heating from 20 °C to 50 °C. Heating/cooling rate: 1 °C/min. Frequency: 1 rad/s. Strain amplitude: 1% 103
Figure 4.19: Variations of modulus G’ and G” as a function of temperature during cooling from 50 °C to 20 °C for 25% HHSS24 alone and in combination with κ-carrageenan. G”: filled symbols; G’: empty symbols. Cooling rate: 1 °C/min. Frequency: 1 rad/s. Strain amplitude: 1% 105
Figure 4.20: Variations of modulus G’ and G” as a function of temperature during cooling from 50 °C to 20 °C for 1% κ-carrageenan and 25% starch mixtures. G’: empty symbols; G”: filled symbols. Cooling rate: 1 °C/min. Frequency: 1 rad/s. Strain amplitude: 1% 106
Figure 4.21: Variations of modulus G’ and G” as a function of temperature during heating from 20 °C to 60 °C for 1% κ-carrageenan and 25% starch mixtures. G’: empty symbols; G”: filled symbols. Cooling rate: 1 °C/min. Frequency: 1 rad/s. Strain amplitude: 1% 107
Figure 4.22: Mechanical spectra of κC1 (■, □), κC0.75 (●, ○) and κC0.5 (▲, Δ). G’: filled symbols, G”: empty symbols. Temperature: 20 ° C. Strain amplitude: 1%. 108
Figure 4. 23: Mechanical spectrum of κC0.5 (●, ○), 25% HHSS12 (dashed line with ▲, Δ) and the mixture of κC0.5-HHSS12 (■, □) at 20°C. G’: filled symbols, G”: empty symbols. Strain amplitude: 0.1% for mixtures and 1% for constituents. 109
Figure 4.24: Mechanical spectrum of mixtures HHSS12-κC1(▲, Δ), HHSS12-κC0.5 (dashed line with ●, ○) and HHSS12-κC0.25 (■, □) at 20 °C. G’: filled symbols, G”: empty symbols. Strain amplitude: 0.1% 110
With the goal of finding an alternative to gelatin in the processing of pharmaceutical capsules, the effects of k-carrageenans on dually modified cassava starch were investigated. While film forming and mechanical properties are important in all pharmaceutical capsules, solubility at high solid concentration and thermo-reversibility are important factors for hard capsule processing. Casava starches were modified first by hydrochloric acid (0.14 N for 6, 12, 18, and 24 h at 50 °C) and secondly by propylene oxide (10, 20, and 30% of solid for 24 h at 40°C).
To improve the gel setting property of the dually modified starch, dually modified cassava starches were combined with -carrageenan (0.25, 0.5, 0.75, and, 1%). The concentration of the K+ ion in the composite mixture was adjusted appropriately to achieve the same sol-gel transition temperature. The rheological properties of the mixtures were measured and compared, with gelatin as the reference material. The solution viscosity, sol-gel transition, and mechanical properties of the films made from the mixtures at 50 °C were comparable to those of gelatin. The viscoelastic moduli (G’ and G”) for the gel mixtures were lower than those of gelatin. The composite gels had temperatures of gelation similar to that of gelatin. Both viscosity in solution and stiffness in gels could be adjusted using high levels of κ-carrageenan and was relatively independent of the molecular weight of the starch. These results illustrate that dually modified cassava starch in combination with -carrageenan has properties similar to those of gelatin, thus these starches can be used in dip-molding processes, such as those used to make pharmaceutical hard capsules.
CHAPTER 1: INTRODUCTION
The capsule is one of the formulations of the oldest pharmaceutical in history, known especially from the ancient Egyptians. In Europe, it was not until the nineteenth century that the first gelatin pharmaceutical capsule with the patent of Mr. Dublanc pharmacist and his student Mr. Mothes. Over the years, this invention has been so successful that the production of capsules has grown rapidly in many countries. This has led to many improvements including the invention of hard gelatin capsules in 1846 by Mr. Lehuby (Podczeck & Jones, 2004).
The development of pharmaceutical capsules, used for therapeutic purposes, originates in the keen interest shown by the numerous researches in pharmacology. This has greatly expanded the range of possible formulations using pharmaceutical capsules. Today, pharmaceutical capsules are mainly based on animal gelatin from porcine or bovine. Gelatin is an animal protein that is a traditional ingredient in many fields, including food. Gelation properties at temperatures close to room temperature and formation of homogeneous films, potable, gelatin as a choice for the manufacturing of pharmaceutical capsules.
However, the use of animal gelatin in the food and pharmaceutical industry is governed by regulations becoming more stringent. The precautionary principal applied, for example, the risk of transmission by animal gelatin; the bovine spongiform encephalopathy (BSE) has questioned its use. Even if today the rules on the origin of the gelatin are very strict and that gelatin is no longer a risk to health, development of alternative products of interest to pharmaceutical and food industries. The sources from which gelatin can also be problematic for ethical or religious populations. Many people around the world do not consume products made from pork (vegetarians, Hebrews, and Muslims) or beef base (vegetarian Hindus). It is therefore that the replacement of gelatin with other texturing agents of non-animal origin has been much research in recent years.
The most important properties that potable gelatin as capsule forming material are heat sealability of films for soft capsule processing and solubility in high concentration, film formability and thermo-reversibility for making hard capsules.
Starch as a plant based material is one of possible alternative for gelatin due to cost and accessibility. Native starches can form films, but the films have not heat sealability, also starches are non soluble biopolymer, and form non-reversible gels. So changes or supporting the structure likely improve the starch property to consider as gelatin replacement in some cases.
The proposed system is a mixture of starch and T-carrageenan. Starch would give the mixture of film-forming properties and solubility in aqueous and carrageenan bring its ability to gel. The selected starch has focused on the use of such modification(s) on starch that able it to dissolve at temperatures below 100 °C and form stable solutions at high concentrations (≈ 20-30%). The botanical origin of the cassava starch is due to its proper amylose content, which improves mechanical properties of films and availability of this starch in Southeast Asia. The gelling agent has been studied was κ-carrageenan/K+ for its ability to form thermo reversible gels and easily adjustable thermo-physical transition temperatures. The film-forming mixtures were prepared by casting method.
The main objective of this research project is to replace the gelatin with a composite cassava (tapioca) starch film for manufacturing of pharmaceutical capsules especially hard capsules. The idea for hard capsule processing is to develop a new system whose characteristics in the solution and solid state would be closer to existing formulations. The constraints imposed industrial development concentrated formulations (25-30%) prepared at temperatures below 100 °C capable of forming a gel by physical cooling and forming a film after drying.
1.2 Rational of study
The main objective of this research was to replace gelatin with a composite casava starch for the manufacture of pharmaceutical capsules. The methods proposed for hard capsule processing involve creating a starch that has characteristics in the solution and solid states that are similar to those of existing gelatin-based formulations. Any gelatin alternative material would have to meet these criteria: solid concentration of 25–30% w/v, preparation temperature below 100 °C, ability to form a gel by physical cooling, and ability to form a film after drying.
The system proposed herein is a mixture of cassava starch and carrageenan. The starch would provide the film-forming property and solubility in an aqueous environment and the carrageenan is expected to enhance the gelling property and improve the durability of]]>