INTRODUCTION:
Gelatin is a protein-based biopolymer made from collagen (animal protein). The different sources of collagen include animal bones, skins, poultry, and fish. Native collagen is obtained by the physical and chemical hydrolysis to remove the "minerals from bone" and "fat and albuminoids from the skin." When collagen undergoes hydrolysis, its fibrous structure is converted into gelatin, a soft, pliable protein due to the dissolution of the cross-linkages between the polypeptide chains1. Gelatin is stored in a closed container. At room temperature, gelatin retains its properties for a longer duration. If the gelatin powder is exposed to a temperature of >45 °C or RH of >60%, it gradually loses its property to swell and dissolve in water2. It is a multifunctional biopolymer, which is naturally biocompatible and biodegradable3. The dried protein is brittle, vitreous, solid in nature, and slightly yellowish. Also, gelatin powder and hydrogels are odorless and tasteless. Chemically, gelatin is constituted of the amino acids having a sequence of Ala-Gly-Pro-Arg-Gly-Glu-4Hyp-Gly-Pro. It contains various amino acids like glycine, proline, valine, etc. Gelatin is regarded as an incomplete protein because it doesn't include all the essential amino acids except tryptophan within its structure4. It has found extensive applications in various industries like food, pharmaceuticals, cosmetics, and medicine. This can be attributed to the unique properties exhibited by the gelatin hydrogel. The typical pharmaceutical applications of gelatin include the synthesis of matrices for biomedical implants, the coating of medical devices, and injectable formulations. It also has found application as a stabilizer in developing vaccine formulations for viral diseases and tetanus toxin5. Further, it has also been used to develop drug delivery vehicles of different size ranges. Nanoparticles of gelatin have been projected for the delivery of the anti-malarial drug chloroquine phosphate. Herein, the nanoparticle formulations were projected as a vehicle for oral drug delivery6. Also, gelatin nanoparticles have been conjugated for the delivery of the antineoplastic drug doxorubicin. The prepared nanoparticles were used for the treatment of neoplasm, leukemia, and lymphoma7. Injectable microspheres of gelatin have shown grand promise for the controlled and sustained delivery of meloxicam (an ideal anti-inflammatory drug)8.
Improvement in the pharmacokinetics and pharmacodynamics of ciprofloxacin, an antibiotic, has been observed when delivered using gelatin microparticles. The prepared microparticles were found to be useful in pulmonary drug delivery9. Hydrogels made with gelatin have been successfully tested for the transdermal delivery of antineoplastic drugs (e.g., cisplatin and adriamycin) to treat skin cancer10. Gelatin hydrogels have also been employed for the delivery of ketoprofen, a commonly used anti-inflammatory drug. The authors reported that the prepared hydrogels are used for wound dressings and artificial organs11.
Hydroxypropyl methylcellulose (HPMC) is a semisynthetic derivative of cellulose, which is capable of holding a significant volume of water within itself. The polysaccharide is an inert, swellable, viscoelastic, and hydrophilic polymer. It appears as white to off-white and odorless powder. It is commonly used as a film former, binder, excipient, disintegrant, lubricator, and thickener in the food and pharmaceutical industries12. The solubility of HPMC is dependent on their grade. There exist two types of HPMC. HPMC is categorized either as an instant or hot water-soluble type based on its solubility. The instant type HPMC solubilizes readily in cold water, whereas the hot water-soluble type HPMC solubilizes in hot water. The various grades of HPMC include E, K, F, and J. Amongst these, E and K types (E4M, E10M, K4M, and K100M) are described here. The E-type HPMC (i.e., E4M and E10M) are hot water-soluble. On the other hand, the K-type HPMC (i.e., K4M and K100M) belongs to the instant type. The viscosity of the HPMC solution is directly proportional to its molecular weight and inversely related to the temperature of the solution. The extent of substitution of the methoxy and hydroxypropyl units varies in different grades. Like gelatin, HPMC has been used in pharmaceutical industries to develop drug delivery vehicles. HPMC-based floating microparticles were developed with an intention for the distribution of the anti-inflammatory drug over the gastric fluid, nimesulide. The microparticles were used as a vehicle for oral delivery13. Moreover, HPMC-based microspheres have also been formulated to deliver an anti-Human Immunodeficiency Virus (HIV) drug named zidovudine14.
Three-dimensional polymeric cross-linked networks called hydrogels, when absorbing water, generate a meshwork structure that inhibits the matrix's complete solubilization15. Hydrogels can be developed by using a combination of different polymers such as polysaccharides (e.g., HPMC) and proteins (e.g., gelatin). The addition of the crosslinking agent depends upon the method (physical and chemical) used to prepare the hydrogels. In some instances, during gelation, the thermodynamic incompatibility of the two constituent polymers causes phase separation in the mixed biopolymer solution. This leads to two coexisting but separate phases; one is a polysaccharide-enriched phase while the other is a protein-enriched phase. Each separated phase is considered to be enriched with one polymer and is generally regarded as a "water in water" colloidal dispersion type of emulsion. Till now, no study in the literature has prepared and assessed the physicochemical characteristics of the phase-separated hydrogels.16,17
Women can self-administer with minimal interference on body functioning and daily life, and obtain high bioavailability with medications. The vaginal epithelium can avoid the hepatic first-pass effect because it has a vast surface area, is highly vascularized, and is extremely permeable to tiny molecules. Localized vaginal delivery reduces systemic drug toxicities, enables direct therapeutic action, and lessens side effects and dosage frequency by stimulating the release of the drug directly to the targeted location. The vagina seems to be the most effective drug delivery system due to its convenience and lack of surgical intervention.18 According to the theory; it interacts with mucosal surfaces (like those in the vaginal cavity) by interacting with charged sugar groups like sialic acid. As a result, hydrogels made from this mucoadhesive polymer may end up in the mucosal environment of the vagina, where they may cause a prolonged release of medication. Since the vaginal canal has a lower pH (about 4.5) than the rest of the body, the ability to dissolve at low pH aids in the disintegration process of these gels there (7.4).19
In this study, we developed a range of hydrogels using different grades of HPMC and gelatin as constituent polymers. The physicochemical properties of these hydrogel formulations were studied thoroughly using bright-field microscopy, FTIR spectroscopy, mechanical tester, impedance analyzer, swelling study, and moisture analyzer. Ciprofloxacin hydrochloride (CPH), a fluoroquinolone antibiotic was selected as the model drug for this investigation. To investigate the topical delivery of the selected drug to the vaginal canal, hydrogels incorporated with drug were created as a vehicle.
MATERIALS AND METHODS:
Materials:
Gelatin (GT) was acquired from Hi-Media Laboratories Pvt. Ltd., Mumbai, India. HPMC was purchased from Colorcon Asia Pvt. Ltd., Goa, India. Ciprofloxacin Hydrochloride (CPH) was collected from Aurobindo Pharma Pvt. Ltd., Hyderabad, India. Ethanol was procured from Changshu Yangyuan Chemical Corporation, China. HCl and glutaraldehyde (GA) were acquired from Loba Chemie Chemical Corporation, Mumbai, India. Dialysis membrane was acquired from Hi-Media Laboratories Pvt. Ltd., Mumbai, India.
Preparation of gelatin and gelatin/HPMC-based hydrogels:
Preparation of the HPMC and gelatin solutions:
Aqueous solutions (2% w/w) of different grades of HPMC (i.e., E4M, E10M, K4M, and K100M) were initially prepared. An accurately weighed amount (2 g) of HPMC was slowly added to the already heated distilled water (98 g; 70 ºC) while being continuously stirred at 200 rpm. 20% (w/w) gelatin solution was prepared by dissolving gelatin (20 g) in distilled water (196 g; 80 ºC). Both the solutions, i.e., HPMC and gelatin solutions were then kept in a temperature-controlled water bath (60 ºC).
Preparation of the hydrogels:
The aqueous solutions of HPMC and gelatin were combined to make a variety of hydrogels (60 ºC; 100 rpm; 3 min) (Table 1). 1ml of crosslinking agent [mixture of ethanol (0.5 ml), glutaraldehyde (0.5 ml), and 1N HCl (0.01 ml)] was put into the homogenized mixture and homogenized further for another 10 sec. The mixtures were then poured into the molds. The gelation process was promoted by keeping the molds at room temperature (25 oC) for 1 h. Then, the formed hydrogels were transferred to a thermal cabinet (5 oC) for storage and further use. CPH was used as a model drug. Hydrogels incorporated with drug were fabricated by dissolving CPH (0.5% w/w) in different HPMC solutions while the remaining preparation procedure are the same as control hydrogels20.
Table 1: Formulation of hydrogels
|
Formulation |
Gelatin solution (g) |
HPMC solution (g) |
Crosslinker (ml) |
CPH (g) |
|
GT |
20 |
0 |
1 |
-- |
|
E1 |
18 |
2 (E4M) |
1 |
-- |
|
K1 |
18 |
2 (K4M) |
1 |
-- |
|
E2 |
18 |
2 (E10M) |
1 |
-- |
|
K2 |
18 |
2 (K100M) |
1 |
-- |
|
GTC |
20 |
0 |
1 |
0.1 |
|
E1C |
18 |
2 (E4M) |
1 |
0.1 |
|
K1C |
18 |
2 (K4M) |
1 |
0.1 |
|
E2C |
18 |
2 (E10M) |
1 |
0.1 |
|
K2C |
18 |
2 (K100M) |
1 |
0.1 |
Microscopy study:
Under a strong bright lighted microscope (Leica Microsystems, model: DM750, GmbH, Germany), the microstructural characteristics of the produced hydrogels were observed and analyzed. A single drop of the liquid combination was put on top of the glass slide, and covered with a coverslip until it was ready for visualization21.
Fourier transform infrared spectroscopy (FTIR) analysis:
The FTIR spectra of the standard gelatin and gelatin/HPMC-based hydrogels were recorded using the FTIR spectrophotometer (Alpha-E, Bruker, Germany) in attenuated reflectance (ATR) mode. The instrument was attached to the ATR module (ATR crystal of ZnSe). The spectra of the prepared hydrogels were developed in the wavenumber range of 4500-500 cm-1 at a resolution of 4 cm-1.
Mechanical study (Stress relaxation study):
The stress relaxation studies of the prepared phase separated hydrogels were investigated by mechanical analyzer. The hydrogels were developed in cylindrical molds (height: 25 mm; diameter: 13 mm), which were used to conduct stress relaxation study. The hydrogels were evaluated by compressing the cylindrical hydrogel with a 30 mm diameter flat probe at a 1.0 mm/s test speed. After applying a trigger force of 5 g, the flat probe compressed the hydrogels by a distance of 5 mm17. Thereafter, the relaxation in the force values was monitored for 60 sec. The experiment was conducted in triplicate.
Electrical/Impedance study:
To investigate the hydrogels' electrical properties (National Instruments, USA), we looked at them with the equipment known as NI-ELVIS-II. Within the confines of two stainless steel electrodes, the hydrogels were kept. (Diameter: 10 mm, spacing between electrodes: 10 mm). After that, measurements of the impedance characteristics were taken at frequencies ranging from 8 Hz to 8 kHz20.
Swelling study:
The cylindrical hydrogels were cut into small pieces of weight 0.15 g. Subsequently, the pieces of the hydrogels were immersed in two types of aqueous media: Phosphate-citrate buffer (pH 3.8) solution and phosphate buffer (pH 6.8) solution. The weight of the hydrogels was then measured every 15 min for 1 h and every 30 min for successive 5 h. The study was continued for 24 hr to determine the equilibrium weight of hydrogels in triplicate. The percentage swelling was computed using the equation below:
Wt -Wi
Percentage Swelling (%) = ------------- x 100
Wi ……. (1)
Where Wt is the weight of the sample at time t and Wi is the initial weight of the sample. Wi indicates the weight of the sample at the beginning of the experiment.
Moisture analysis:
The moisture content of the prepared hydrogels was analyzed using a moisture analyzer (WENSAR PGB 1MB Labman, Tamilnadu, India). 1 g of hydrogels was dried in the moisture analyzer at 180 ºC. The analysis was performed in triplicate for each formulation.
In vitro Dissolution Study:
Using Franz's diffusion cell, we experimentally examined the drug release profile of the selected drug from the produced hydrogels. 20 ml of phosphate buffer was placed in the diffusion cell's receptor compartment. (PBS; pH 6.8). Between the diffusion cell's donor and receptor halves, a dialysis membrane has been permanently installed. Hydrogel formulations of 0.5 g were applied to the membrane (diffusion area: 1.64 cm2) at 37 °C. At predetermined intervals, 1 ml samples were taken from the receptor compartment. (5, 15, 30, 45, 60, 90, 120, 150, 180 min). Fresh PBS (pH 6.8) was used to replace the withdrawn sample. We measured the amount of drug in the receptor compartment by analyzing the collected samples with a UV-Spectrophotometer (wavelength: 277 nm; Model: 1700, Shimadzu, Japan).
RESULTS AND DISCUSSION:
Hydrogel preparation:
Phase separated hydrogels are a unique type of polymer
blend in which multiple polymer within the mixture segregate into distinct
polymeric phases. The process of phase separation can take place in a variety
of ways, mainly due to inter- or intra-polymeric interactions. There are three
different forms of biopolymeric phase separation: segregative, associative, and
bicontinuous phase separation16. Negative (-ve) interactions between
the two polymeric phases induce segregative phase separation. The molecular dynamics
present in the segregative phase separation process was changed due to the
affinity of solvents towards polymers, leading to the formation of two
different phases. The associative phase separation, on the other hand, takes
place in a system where the contacts between the two polymers are robust. The
associative interaction results in the expulsion of the solvent to form the
dispersion phase. The third type of phase separation, bicontinuous phase
separation, results in the formation of gelled systems wherein both the polymer
phases appear to be present as distinct phases, yet both appear to form
continuum phases. In our study, the gelatin/HPMC-based hydrogels were created
by the segregative phase-separation mechanism. The physical stability of the hydrogels
was enhanced by crosslinking them with glutaraldehyde. The schematic
representation of hydrogel preparation and pictograph of the hydrogels in the
form of cylindrical shapes has been shown in Figure 1 & Figure 2
respectively. As observed
from
the figure, the hydrogels appeared lightly brown/pale yellowish. Moreover, the
formulations were smooth and silky to the touch and had a super cooling
sensation.
Figure 1: Schematic representation of the hydrogels for vaginal drug delivery applications
Figure 2: Prepared hydrogels: (a) GT, (b) E1, (c) K1, (d) E2, and (e) K2
Microscopy study:
Globular formations were visible in the hydrogels' micrographs, and they looked to be evenly dispersed throughout the continuous gelatin phase (Figure 3). The size of the globules was found to get increased with a rise in the viscosity of the HPMC. It can be the result of intra-polymer interactions that occurred during formulation. The intra-polymer interactions16 of Gelatin/HPMC K100M (i.e., K2) hydrogels was found to be greater due to the large globule size of the dispersed phase.
Figure 3: Bright field micrographs of the prepared hydrogels: (a) GT, (b) E1, (c) K1, (d) E2, and (e) K2
Fourier transform infrared spectroscopy (FTIR) analysis:
Figure 4 shows the FTIR spectra of the hydrogels, which were taken in the attenuated total reflectance (ATR) mode. The existence of inter/intramolecular hydrogen bonding inside the gelatin hydrogel (GT) matrix could explain the broad peak obtained at 3342 cm-1. N-H stretching vibrations are connected with this peak. The hydrogen bonding in gelatin hydrogels is caused by the presence of –OH, –NH, and –COOH groups. The presence of protein molecules was suggested by the existence of dual peaks at 1636 cm-1 and 1555 cm-1. The peak position of 1636 cm-1 is connected to amide-I absorption, caused by the stretching of C=O in the amide groups. The peak position of 1555 cm-1 is related to amide-II absorption, caused by the combination of the N-H bending vibration and the amide C-N bond stretching vibration17,18. On the other hand, the spectra's peak at 1244 cm-1 may have been caused by amide-III bonds.
Figure 4: FTIR spectra of the prepared hydrogels: (a) GT, (b) E1, (c) K1, (d) E2, and (e) K2
It implied that when the protein molecules were transformed into hydrogels, their secondary structure remained unchanged. In the case of gelatin/HPMC-based hydrogels, the spectra of the hydrogels containing lower viscosity HPMC polymer (i.e., E4M and K4M),) showed no changes in the position of the vibrational signals verified at ~1648 cm-1, ~1636 cm-1, ~1634 cm-1, ~1636 cm-1. However, the spectra of hydrogels prepared with higher viscosity HPMC polymer (i.e., E10M and K100M), the peak attributed to amide-I absorption shifted towards the higher wavenumber. Such type of shift suggested the presence of interaction between the COO- groups of the polysaccharide and the amide-I group of the gelatin.
Table 2. Calculated area under the peak observed in the wavenumber ranging from 3800-2850 cm-1
|
Formulations |
Area under the peak |
|
GT |
-44.720±17.731 |
|
E1 |
-81.620±26.273 |
|
K1 |
-76.646±21.540 |
|
E2 |
-64.549±33.270 |
|
K2 |
-70.901±88.056 |
The degree of hydrogen bonding between the hydrogels covering polysaccharides was observed in the wavenumber range of 3700-2900 cm-1. The AUC of gelatin/HPMC-based hydrogels is tabulated (Table 2). The results indicated that the polymer HPMC of different grades (and therefore, viscosities) formed intermolecular interactions with gelatin polymer present in the prepared hydrogels. The existence of the free carboxylic acid groups may have caused the HPMC to interact with gelatin.
Mechanical study:
Figure 5: Stress relaxation study of the prepared hydrogels: (a) Stress relaxation profiles, (b) F0 profile, (c) F60 profile, and (d) % SR profile
Using the stress relaxation (SR) method, the hydrogels' viscoelastic characteristics were evaluated (Figure. 5a). The firmness (F0; peak force at the end of the compression stage) of the hydrogels increased along with the viscosity of the HPMC in the formulations (Table 3; Figure 5b). The firmness parameter (F0) was found to be significantly higher in GT in comparison to the HPMC-containing hydrogels (p<0.05). The presence of numerous protein-protein interactions in the standard hydrogel might be the reason for its high firmness. However, in the case of gelatin/HPMC-based hydrogels, the inclusion of different grades of HPMC (i.e., a polysaccharide phase) in the gelatin matrix might have an occurrence in the reduction of protein-protein interactions. This may account for the hydrogels containing HPMC having lower firmness values than GT.
Table 3. Stress relaxation study of hydrogels
|
Formulations |
F0 (g) |
F60 (g) |
% SR |
|
GT |
273.83 ± 16.85 |
253.40 ± 11.35 |
7.39 ± 1.62 |
|
E1 |
160.20 ± 13.84 |
148.52 ± 12.28 |
7.27 ± 0.41 |
|
K1 |
163.96 ± 0.73 |
153.39 ± 1.08 |
6.44 ± 0.51 |
|
E2 |
224.69 ± 25.89 |
213.41 ± 24.57 |
5.01 ± 0.18 |
|
K2 |
162.46 ± 49.47 |
144.41 ± 51.96 |
12.00 ± 4.51 |
Figure 5a shows that the SR profiles descended exponentially to a residual force (F60) that represents the mechanical stability of the formulations over extended periods (Figure 5c; Table 3). Similar to the F0 profile, the residual force parameter was the highest for GT. Among HPMC-containing hydrogels, the F0 and F60 parameters were observed to be higher and lower for gelatin/HPMC E100M (E2) hydrogel, respectively. The percentage stress relaxation (% SR) of GT was similar to E1, K1, and K2 hydrogels (p>0.05) while it was comparatively higher than E2 hydrogel (p<0.05) (Figure 5d; Table 3). All HPMC-containing hydrogels, except E1, showed significantly lower % SR than K2 (p<0.05). Hence, it can be concluded that the high viscosity of HPMC K100M increased the viscoelastic fluid component in K2 hydrogel.
Electrical/Impedance study:
Figure 6: Electric impedance profiles of the prepared hydrogels
It is clear from the impedance spectra shown in Figure 6 that at low frequencies, the impedance of the hydrogels E2 and K2 was nearly equal but higher than the impedance of the other remaining cylindrical hydrogels. Among all hydrogels, the property of electrical impedance of the HPMC-containing hydrogels was observed to be greater than GT. This showed an enhanced conductivity of the hydrogel due to the inclusion of polysaccharides in the gelatin polymer matrix. The capability of polysaccharides to store more bound water than gelatin molecules, as predicted by our swelling research, can help to explain it. The impedance properties of the spherical hydrogels were comparable. At lower frequencies, the molds revealed higher impedances, which quickly faded to the residual impedance at higher frequencies. Capacitive dominating materials are known to have this type of profile.
Swelling study:
The water uptake study was done by using a phosphate-citrate buffer (pH 3.8) solution and a phosphate buffer (pH 6.8) solution (Figure 7a, 7b). In this study, gelatin/HPMC hydrogel (K1) swelled faster at pH 3.8 than the other hydrogels (Figure 7a) whereas its swelling ratio was found to be significantly different at pH 6.8 (Figure 7b). The difference in the swelling ratio of the formulation in two different pH solutions might be due to the ionization of the amino groups of the gelatin molecules. At low pH, the ionized amino groups of the gelatin polymer might have caused electrostatic repulsion among the chains of the protein molecule. As a result of this, the polysaccharide (i.e., HPMC) phase of the said hydrogel matrix might have been exposed. Hence, it can be suggested that the porous gelatin polymer network increased the infiltration of water within the hydrogel, which in turn increased the wetting of the polysaccharide phase. This explains the higher swelling ratio of K1 hydrogel at pH 3.8. However, on the other hand, the carboxylic and amino groups persisted as zwitterions at near-neutral pH (pH 6.8) owing to which the gelatin polymer acquired a neutral state. As a result, at this pH, the polysaccharide phase's ability to absorb water molecules was the primary factor in determining the swelling behavior of the hydrogel formulations. As shown in Figure 7, the foregoing process significantly impacted the water molecule absorption within the hydrogel in response to changes in polysaccharide content.
Figure 7: Swelling behavior of the prepared hydrogels immersed in different pH solutions: (a) Swelling ratio profiles in pH 3.8) and (b) Swelling ratio profiles in PBS (pH 6.8)
The swelling profile of the gelatin/HPMC-based hydrogels indicated that swelling was pH-dependent. The hydrogels with a lower HPMC viscosity swelled more at pH 3.8, and vice versa. It is possible to explain the swelling of these hydrogels due to the combined electrostatic events that are taking on at both of the polymeric phases. At a pH of 3.8, the amino groups in gelatin were ionized, but the shielding effect of the polysaccharide phase was more evident because of the presence of free carboxylic groups. Lesser grade of HPMC utilized, decreased the size of the polysaccharide phase and enabled a greater amount of swelling media to be absorbed. Therefore, the findings suggest that the increase in the viscosity of the polysaccharide phase is responsible for the decrease in swelling observed at a pH of 3.8 for the hydrogels. At pH 6.8, a reversal of swelling behavior was seen. On comparing the HPMC-containing hydrogels with GT at pH 6.8, the swelling ratio of the E1 and K1 hydrogels was observed to be greater (Figure 7b). The difference was discovered in the middle and became minor when the pH was near neutral.
Moisture analysis:
Figure 8: Moisture analysis of the prepared hydrogels: (a) % M content and (b) Time data
The percentage Moisture (% M) content of the standard gelatin hydrogels and remaining gelatin/HPMC-based formulations (i.e., E1, K1, E2, and K2) was found to be in the range of 80-85% (Figure 8a, Table 4).
Table 4. Moisture analysis data of the prepared hydrogels
|
Parameters |
GT |
E1 |
K1 |
E2 |
K2 |
|
Time |
13.506±4.109 |
14.996±3.862 |
13.726±1.727 |
14.513±2.030 |
13.693±3.286 |
|
% M |
84.653±4.005 |
82.936±1.101 |
83.156±0.447 |
80.986±2.754 |
83.633±0.875 |
The % M content of the prepared hydrogels was taken for the time in an average of 13 to 14 min (Figure 8b, Table 4). As observed from the graph, the results showed that the % M content of the formulations was statistically insignificant (p>0.05). Therefore, the hydrogels can be stored for a long time due to their high moisture content.
In vitro Drug Release Study:
The Ciprofloxacin loaded hydrogels with gelatin, different grades of HPMC (i.e., E4M, E10M, K4M, and K100M) were designated as GTC, E1C, K1C, E2C, and K2C respectively. The CPH release from standard GTC hydrogel and phase-separated gelatin/HPMC-based hydrogels was studied at pH 6.8 to examine the properties of molecular weight of HPMC. The CPDR (cumulative percent drug release) of CPH was observed to be the highest (9.22 ± 0.16%) in GTC after 180 minutes (Figure 9). HPMC-containing hydrogels showed a reduction in CPDR as compared to the control formulation (GTC). The CPDR from E1C, K1C, E2C, and K2C were found as 3.24 ± 0.10%, 2.78 ± 0.22%, 3.89 ± 0.20%, and 1.97 ± 0.07%, respectively. It was observed that the CPDR of CPH in all gelatin/HPMC-based hydrogels was significantly lower in comparison to that of GTC (p<0.05). Moreover, the differences in the percent release of CPH in HPMC-containing hydrogels, namely, E1C and K1C, were not statistically significant (p>0.05).
Figure 9: Drug release profiles of the CPH-loaded hydrogels
On an overall basis, the lower CPDR observed in HPMC-containing formulations in contrast to GTC could be accounted for the swelling properties of HPMC. This is consistent with the findings of our swelling study. The expansion of the polysaccharide phase (i.e., HPMC) due to swelling might have formed a gelled network structure, out of which the release of the drug was very likely difficult. This could have extended the drug's diffusional path length19, and therefore, slowed down the CPDR rate of the model drug that was produced by hydrogels containing HPMC.
CONCLUSION:
This study explores the development of pH-sensitive hydrogels from gelatin and hydroxypropyl methylcellulose (HPMC) for intravaginal drug delivery. These hydrogels degrade after use, enhancing user acceptance. Phase-separated hydrogels were prepared by varying the viscosity of HPMC (E4M, E10M, K4M, K100M), which displayed a color ranging from light brown to yellow. Hydrogels were soft, flexible, and contained globules embedded within a gelatin matrix. FTIR spectroscopy showed stronger hydrogen bonds in gelatin/HPMC hydrogels compared to those made of only gelatin. While the inclusion of HPMC reduced the firmness and increased the swelling ratio of the hydrogels, it also enhanced their water retention and conductivity. Swelling behavior varied with pH: at acidic pH (3.8), hydrogels with lower HPMC content absorbed more water, while the opposite occurred at neutral pH (6.8). The hydrogels formulations with gelatin/HPMC exhibited sustained drug release, suggesting their potential as effective drug delivery systems.
ABBREVIATIONS:
RH: Relative humidity; g: Gram; mg: Mili gram; mm: Milli Meter; ml: Milli Liter; cm: Centi Meter; % w/w: Percentage Weight By Weight; rpm: Revolution Per Minute; °C: Degree Centigrade; mmol: Milli Moles; μm: Micrometre; nm: Nanometre; mPa. s: Milli Pascal-Second; kV: Kilo Volt; min: Minute; cm-1; Per Centimetre.
ACKNOWLEDGEMENT:
Ethical statement:
This material is the author's original work, which has not been previously published elsewhere. Research involving human participants and/or animals is not used in this current study.
CONFLICT OF INTEREST:
All the authors declared that there is no conflict of interest.
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Received on 13.12.2024 Revised on 19.04.2025 Accepted on 22.07.2025 Published on 08.11.2025 Available online from November 13, 2025 Research J. Pharmacy and Technology. 2025;18(11):5377-5384. DOI: 10.52711/0974-360X.2025.00775 © RJPT All right reserved
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