In vitro release studies of flurbiprofen from different topical formulations

The release profiles of flurbiprofen (F) from different gel and ointment formulations were studied in order to evaluate factors governing the release process. Carbopol 934P (CAB), poloxamer 407 (POL), and eudragit S100 (EUD) gel bases were used, while emulsion (EML) and polyethylene glycol (PEG) ointments were employed. The release studies were conducted using membraneless diffusion cells and lipophilic receptor medium, isopropyl myristate (IPM). The effects of gelling agent concentrations and the initial drug load on drug release were determined. Hydrogels were observed to give higher amounts of drug release than hydrophobic EUD gel and ointments, despite the lower bulk viscosity of these bases. Flurbiprofen release from CAB gels was 3.06-1.56-fold higher than from other formulations. Over a 4-hr period, the amount of F released was 492.8 and 316.0 µg/cm² from 2% CAB and 25% POL gels, while it was 213.05, 168.61, and 160.9 µg/cm² from EML, 40% EUD, and PEG bases, respectively. The diffusivity of F in the gel bases was an inverse function of the polymer concentrations over the range of 1-3% CAB, 20-30% POL, and 35-45% EUD gels. Drug release was increased from the bases as the initial F concentration increased over the range 0.25-1.0%, while the diffusion coefficient observed an inverse relationship. The CAB and POL gels could be the vehicles of choice for the rapid release and onset of F after topical application.     

Carboxymethyl Mungbean Starch as a New Pharmaceutical Gelling Agent for Topical Preparation

An application of carboxymethyl mungbean starch (CMMS) as a gelling agent in the topical pharmaceutical preparation was investigated. CMMS was prepared using specific conditions that yielded a high-viscosity product. Polymer gels and gel bases were prepared at 1–10% (wt/wt), and physicochemical studies were carried out in comparison with four standard gelling agents: carbopol 940 (CP), hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC), and sodium carboxymethyl cellulose (SCMC). Piroxicam was used as a model drug to study the drug release profile of the gel formulations. The tackless, greaseless, and transparent CMMS gels exhibited pseudoplastic behavior with thixotropy at concentrations less than 5% (wt/wt). At a concentration of 5% (wt/wt) and higher, the semisolid gels showed plastic flow characteristics. Viscosity and X-ray diffraction results indicated a good compatibility between CMMS and the acidic piroxicam. No precipitation of piroxicam or phase separation was observed during a stability test. The release rate of piroxicam from 3% (wt/wt) CMMS gel was 1,003.79 ± 105.08 μg/cm², which was comparable with 947.66 ± 133.70 μg/cm² obtained from a 0.5% (wt/wt) carbopol formulation. The release profiles of both formulations were consistent and remained unchanged after 2 months' storage. Viscosity played an important role in controlling the release rate of low concentration CMMS formulations by regulating the drug diffusion. At a concentration of 5% (wt/wt) CMMS and higher, the release rates of piroxicam were not significantly different. A plausible explanation based on the nature of the gelling agent was proposed. Stability and drug release profiles of CMMS and commercial gelling agents were compared. The results supported the potential use of CMMS as a new, effective gelling agent for topical gel preparation.     

Mucoadhesive Polymeric Hydrogels for Nasal Delivery of Acyclovir

The study evaluated different mucoadhesive polymeric hydrogels for nasal delivery of acyclovir. Gels containing poly-N-vinyl-2-pyrrolidone (PVP) were prepared with crosslinking achieved by irradiation with a radiation dose of 15 kGy being as efficient as 20 kGy. Gels containing chitosan and carbopol were also evaluated. The mucoadhesive properties of gels were measured by a modification of a classical tensile experiment, employing a tensile tester and using freshly excised sheep nasal mucosa. Considering the mucoadhesive force, chitosan gel and gel prepared with 3% PVP in presence of polyethylene glycol (PEG) 600 were the most efficient. The in vitro drug release depended on the gel composition. Higher release rates were obtained from PVP gels compared to chitosan or carbopol gels. The release rate of drug from PVP gels was increased further in presence of PEG or glycerol. Histopathological investigations proved that the PVP was a safe hydrogel to be used for mucosal delivery. The PEG in gel formulations caused less damages to the nasal mucosal compared to formulation containing glycerol.     

Semisolid matrix filled capsules: an approach to improve dissolution stability of phenytoin sodium formulation

Seven semisolid fill bases were selected for the formulation of 24 capsule formulations, each containing 100 mg of phenytoin sodium. The fill materials were selected based on the water absorption capacity of their mixtures with phenytoin sodium. The fill matrices included lipophilic bases (castor oil, soya oil, and Gelucire (G) 33/01), amphiphilic bases (G 44/14 and Suppocire BP), and water-soluble bases (PEG 4000 and PEG 6000). The drug:base ratio was 1:2. Excipients such as lecithin, docusate sodium, and poloxamer 188 were added to some formulations. The dissolution rate study indicated that formulations containing lipophilic and amphiphilic bases showed the best release profiles. These are F4 (castor oil-1% docusate sodium); F10 (castor oil-3% poloxamer 188); F14 (G33/01-10% lecithin); F17 (G33/01-1% docusate sodium), and F20 (Suppocire BP). Further, the dissolution stability of the five formulations above was assessed by an accelerated stability study at 30°C and 75% RH using standard Epanutin capsules for comparison. The study included the test and standard capsules either packed in the container of marketed Epanutin capsules (packed) or removed from their outer pack (unpacked). Release data indicated superior release rates of castor oil based formulations (F4 and F10) relative to standard capsules in both the unpacked and packed forms. For instance, the extent of drug release at 30 min after 1 month was 91% for F4 and F10 and 20% for standard capsules. Drug release from packed capsules after 6 months storage was 88% for both formulations F4 and F10 and 35% for standard capsules. In conclusion, the pharmaceutical quality of phenytoin sodium capsules can be improved by using a semisolid lipophilic matrix filled in hard gelatin capsules.     

Mucoadhesive polymeric hydrogels for nasal delivery of acyclovir

The study evaluated different mucoadhesive polymeric hydrogels for nasal delivery of acyclovir. Gels containing poly-N-vinyl-2-pyrrolidone (PVP) were prepared with crosslinking achieved by irradiation with a radiation dose of 15 kGy being as efficient as 20 kGy. Gels containing chitosan and carbopol were also evaluated. The mucoadhesive properties of gels were measured by a modification of a classical tensile experiment, employing a tensile tester and using freshly excised sheep nasal mucosa. Considering the mucoadhesive force, chitosan gel and gel prepared with 3% PVP in presence of polyethylene glycol (PEG) 600 were the most efficient. The in vitro drug release depended on the gel composition. Higher release rates were obtained from PVP gels compared to chitosan or carbopol gels. The release rate of drug from PVP gels was increased further in presence of PEG or glycerol. Histopathological investigations proved that the PVP was a safe hydrogel to be used for mucosal delivery. The PEG in gel formulations caused less damages to the nasal mucosal compared to formulation containing glycerol.     

Box–Behnken experimental design for preparation and optimization of the intranasal gels of selegiline hydrochloride

Selegiline hydrochloride (SL) is chosen as an adjunct for the control of clinical signs of Parkinsonian patients. The aim of the present work is to develop and optimize thermosensitive gels using Pluronic (F-127) for enhancing transport of SL into the brain through the nasal route. SL gels were prepared using a cold method and the Box–Behnken experimental design methodology. Drug (SL), gelling agent (F-127), and emulsifier (Propylene glycol, PG) were selected as independent variables, while the gelation temperature, gel strength, pH, gel content, and gel erosion were considered as dependent variables. For further understanding of the interaction between the various variables, contour plots and surface plots were also applied. Selected formulations, like S10 (contain 25?mg SL, 20?g F-127, and 1?g PG) and S14 (contain 50?mg SL, 18?g F-127 and 1?g PG), had a clear appearance in the sol form, with gelling temperature of the nasal gel ranging between 33 and 34, respectively. The gel strength of the formulations varied from 4.67 and 0.68?mm and the drug content was 100%. The pH of the formulations ranged between 6.71 and 7.11. Detachment force was acceptable (63.69–244.16 N/cm²) to provide prolonged adhesion. In vitro, drug release studies showed that the prepared formulations could release SL for up to 8?h. Permeation flux for the S10 gel was 0.0002?mg/min/cm². Results demonstrated that the potential use of SL gels can enhance the therapeutic effect of SL through the intranasal administration.     

Medicament Release From Ointment Bases: V. Naproxen In-Vitro Release and In-Vivo Percutaneous Absorption In Rabbits

Abstract

The in- vitro release of Naproxen from various ointment bases, including a water-washable base with the drug in the water phase (I) and the drug in the oil phase (II), a hydrophilic base with the drug in the water phase (III), and the drug in the oil phase (IV), and an anhydrous ointment (V), a gel (VI) and a modified University of California (U.C.H.) base (VII) were studied. In addition, the effects of various additives (urea, ethanol, dimethyl sulfoxide and polyethylene glycol-400) on the release of Naproxen from formulations (I) and (II) were determined. Low concentrations of urea and ethanol in the formulations increased the release of the drug from both these bases, however, higher concentrations adversely affected the release of the drug. While dimethyl sulfoxide (DMSO) had no significant effect on the drug release, the inclusion of polyethylene glycol-400 in both bases decreased the release of Naproxen.

The percutaneous absorption of Naproxen from the waterwashable base (drug in the oil phase) and hydrophilic base (drug in the oil phase) were studied by applying the ointments on rabbit's skin. It was observed that the bioavailability of Naproxen from the hydrophilic base was slightly greater than that from the water-washable base, and that DMSO had no effect in enhancing the in-vivo release of Naproxen from the ointments evaluated. Using the in-vivo data, the absorption and elimination rate constants, the half-life and AUC were calculated.     

Medicament Release from Ointment Bases: I. Indomethacin. In Vitro and in Vivo Release Studies

The in vitro release of indomethacin from 1%, 3%, and 5% indomethacin ointments and its in vivo absorption through the skin of rabbits was investigated. The in vitro release of indomethacin followed zero-order kinetics and was better from an absorption base ointment. No significant differences (F=3.047 and P=0.079 for the absorption base) and (F=2.15 and P=0.14 for the hydrophilic base) in the release rate of indomethacin in 1%, 3%, and 5% indomethacin ointments were observed. Indomethacin was most effectively absorbed from absorption ointment bases. A correlation between the in vitro release and the in vivo absorption was found; also, a correlation between the in vivo release pattern of the bases used and the in vivo data reported in the literature was observed.     

Medicament Release From Ointment Bases: V. Naproxen In-Vitro Release and In-Vivo Percutaneous Absorption In Rabbits

The in- vitro release of Naproxen from various ointment bases, including a water-washable base with the drug in the water phase (I) and the drug in the oil phase (II), a hydrophilic base with the drug in the water phase (III), and the drug in the oil phase (IV), and an anhydrous ointment (V), a gel (VI) and a modified University of California (U .C .H.) base (VII) were studied. In addition, the effects of various additives (urea, ethanol, dimethyl sulfoxide and polyethylene glycol-400) on the release of Naproxen from formulations (I) and (II) were determined. Low concentrations of urea and ethanol in the formulations increased the release of the drug from both these bases, however, higher concentrations adversely affected the release of the drug. While dimethyl sulfoxide (DMSO) had no significant effect on the drug release, the inclusion of polyethylene glycol-400 in both bases decreased the release of Naproxen.

The percutaneous absorption of Naproxen from the waterwashable base (drug in the oil phase) and hydrophilic base (drug in the oil phase) were studied by applying the ointments on rabbit's skin. It was observed that the bioavailability of Naproxen from the hydrophilic base was slightly greater than that from the water-washable base, and that DMSO had no effect in enhancing the in-vivo release of Naproxen from the ointments evaluated. Using the in-vivo data, the absorption and elimination rate constants, the half-life and AUC were calculated.     

Medicament Release from Ointment Bases: I. Indomethacin. In Vitro and in Vivo Release Studies

Abstract

The in vitro release of indomethacin from 1%, 3%, and 5% indomethacin ointments and its in vivo absorption through the skin of rabbits was investigated. The in vitro release of indomethacin followed zero-order kinetics and was better from an absorption base ointment. No significant differences (F=3.047 and P=0.079 for the absorption base) and (F=2.15 and P=0.14 for the hydrophilic base) in the release rate of indomethacin in 1%, 3%, and 5% indomethacin ointments were observed. Indomethacin was most effectively absorbed from absorption ointment bases. A correlation between the in vitro release and the in vivo absorption was found; also, a correlation between the in vivo release pattern of the bases used and the in vivo data reported in the literature was observed.     

In vitro release properties of caffeine. I. effect of concentration and type of ointment base

Abstract

Caffeine has recently been found to cure atopic dermatitis, presumably by increasing skin levels of cAMP.In the light of these findings, its release from different ointment bases at varying concentrations was investigated in vitro. The ointment bases used were a petrolatum (named as petrolatum A), a PEG ointment (USP XVIII), a hydrophilic ointment (USP XVIII), and a w/o type emulsifying ointment. It was incorporated into ointment bases at 1,5,10,20 and 30% (w/w) concentrations, by simple trituration technique.

Release experiments were carried out at 37°C, with diffusion cells which were placed in distilled water filled beakers.

For all caffeine concentrations used, the release was highest from the PEG ointment. It decreased with the hydrophilic ointment, the emulsifying ointment, and petrolatum A, in that order. From both petrolatum base and the PEG ointment, release of caffeine increased significantly with increasing concentrations. As for the hydrophilic and emulsifying ointments, release patterns were found to be independent of concentration for some percentages of caffeine.     

In vitro release properties of caffeine. I. effect of concentration and type of ointment base

Caffeine has recently been found to cure atopic dermatitis, presumably by increasing skin levels of cAMP.In the light of these findings, its release from different ointment bases at varying concentrations was investigated in vitro. The ointment bases used were a petrolatum (named as petrolatum A), a PEG ointment (USP XVIII), a hydrophilic ointment (USP XVIII), and a w/o type emulsifying ointment. It was incorporated into ointment bases at 1,5,10,20 and 30% (w/w) concentrations, by simple trituration technique.

Release experiments were carried out at 37°C, with diffusion cells which were placed in distilled water filled beakers.

For all caffeine concentrations used, the release was highest from the PEG ointment. It decreased with the hydrophilic ointment, the emulsifying ointment, and petrolatum A, in that order. From both petrolatum base and the PEG ointment, release of caffeine increased significantly with increasing concentrations. As for the hydrophilic and emulsifying ointments, release patterns were found to be independent of concentration for some percentages of caffeine.     

Characterization and evaluation of β-glucan formulations as injectable implants for protein and peptide delivery

Context: Injectable implants are biodegradable, syringeable formulations that are injected as liquids, but form a gel inside the body due to a change in pH, ions or temperature. Objective: To investigate the effect of polymer concentration, pH, ions and temperature on the gel formation of β-glucan, a natural cell-wall polysaccharide derived from barley, with particular emphasis on two-phase system formation after addition of dextran or PEG. Materials and methods: Oscillation viscometry was used to evaluate the gel character by measuring flow index (N), storage (G') and loss (G″) moduli. Two-phase systems were further characterized for hardness and syringeability using a texture analyzer. Finally, in vitro release characteristics were determined using Franz diffusion cells. Results: Oscillation viscometry revealed that only addition of dextran or PEG resulted in distinct gel formation. This was seen by a decrease in N after polymer addition. Moreover, hardness (in g) of the gels increased significantly (p?相似文献   

Design and development of a safer non-invasive transungual drug delivery system for topical treatment of onychomycosis

Objective: The main objective of this study is to develop a safer non-invasive treatment for nail infections since the current treatment regimen has drawbacks like, incidence of systemic side-effects and higher cost. Proposed topical treatment on the other hand can drastically improve the situation, hence highly desirable. This work was undertaken with a hypothesis to develop a transungual microemulsion gel for topical treatment of onychomycosis.

Methods: Benzyl alcohol and isopropyl myristate were used as oil, Pluronic F68 as surfactant and ethanol as co surfactant, in double-distilled water and loading itraconazole as the model antifungal drug. Pseudo-ternary phase diagram was developed by titrating different ratios of total oil and water with total surfactant, and K_m ratio was fixed at 1:1. Microemulsion formulations were prepared based on the phase diagram and incorporated in gels by adding Carbopol 934P. Nail permeation enhancers like urea and salicylic acid were used to increase drug permeation through the nail plate. Parameters like drug loading, clarity, particle size distribution, drug entrapment efficiency (DEE), drug release profile, release kinetics and nail uptake were checked for the evaluation of the formulations.

Results: Complete release of drug from the formulation varied from 60 to 120?min. The optimized formulation had DEE of 92.75%, complete drug release in 60?min and highest nail uptake of 0.386%/mm² (39?µg of drug) with 5% urea as nail permeation enhancer.

Conclusion: The formulation may prove beneficial in safer treatment of onychomycosis.     

Carboxymethyl mungbean starch as a new pharmaceutical gelling agent for topical preparation

An application of carboxymethyl mungbean starch (CMMS) as a gelling agent in the topical pharmaceutical preparation was investigated. CMMS was prepared using specific conditions that yielded a high-viscosity product. Polymer gels and gel bases were prepared at 1-10% (wt/wt), and physicochemical studies were carried out in comparison with four standard gelling agents: carbopol 940 (CP), hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC), and sodium carboxymethyl cellulose (SCMC). Piroxicam was used as a model drug to study the drug release profile of the gel formulations. The tackless, greaseless, and transparent CMMS gels exhibited pseudoplastic behavior with thixotropy at concentrations less than 5% (wt/wt). At a concentration of 5% (wt/wt) and higher, the semisolid gels showed plastic flow characteristics. Viscosity and X-ray diffraction results indicated a good compatibility between CMMS and the acidic piroxicam. No precipitation of piroxicam or phase separation was observed during a stability test. The release rate of piroxicam from 3% (wt/wt) CMMS gel was 1,003.79 +/- 105.08 microg/cm(2), which was comparable with 947.66 +/- 133.70 microg/cm(2) obtained from a 0.5% (wt/wt) carbopol formulation. The release profiles of both formulations were consistent and remained unchanged after 2 months' storage. Viscosity played an important role in controlling the release rate of low concentration CMMS formulations by regulating the drug diffusion. At a concentration of 5% (wt/wt) CMMS and higher, the release rates of piroxicam were not significantly different. A plausible explanation based on the nature of the gelling agent was proposed. Stability and drug release profiles of CMMS and commercial gelling agents were compared. The results supported the potential use of CMMS as a new, effective gelling agent for topical gel preparation.     

In Vitro Release and Diffusion Studies of Promethazine Hydrochloride from Polymeric Dermatological Bases Using Cellulose Membrane and Hairless Mouse Skin

The study was designed to investigate the feasibility of developing a transdermal drug dosage form of promethazine hydrochloride (PMH). The in vitro release and diffusion characteristics of PMH from various dermatological polymeric bases were studied using cellulose membrane and hairless mouse skin as the diffusion barriers. These included polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC), cross-linked microcrystalline cellulose, and carboxyl methyl cellulose sodium (Avicel® CL-611), and a modified hydrophilic ointment USP. In addition, the effects of several additive ingredients known to enhance the drug release from topical formulations were evaluated. The general rank order for the drug release from these formulations using cellulose membrane was observed to be PEG > HMPC > Avicel CL-611 > hydrophilic ointment base. The inclusion of the additives had little or no effect on the drug diffusion from these bases, except for the hydrophilic ointment formulation containing 15% ethanol, which provided a significant increase in the drug release. However, when these formulations were studied for drug diffusion through the hairless mouse skin, the Avicel CL-611 base containing 15% ethanol exhibited the optimum drug release. The data also revealed that this formulation gave the highest steady-state flux, diffusion, and permeability coefficient values and correlated well with the amount of drug release.     

Characterization and evaluation of β-glucan formulations as injectable implants for protein and peptide delivery

Context: Injectable implants are biodegradable, syringeable formulations that are injected as liquids, but form a gel inside the body due to a change in pH, ions or temperature.

Objective: To investigate the effect of polymer concentration, pH, ions and temperature on the gel formation of β-glucan, a natural cell-wall polysaccharide derived from barley, with particular emphasis on two-phase system formation after addition of dextran or PEG.

Materials and methods: Oscillation viscometry was used to evaluate the gel character by measuring flow index (N), storage (G′) and loss (G″) moduli. Two-phase systems were further characterized for hardness and syringeability using a texture analyzer. Finally, in vitro release characteristics were determined using Franz diffusion cells.

Results: Oscillation viscometry revealed that only addition of dextran or PEG resulted in distinct gel formation. This was seen by a decrease in N after polymer addition. Moreover, hardness (in g) of the gels increased significantly (p?<?0.001) from 3.65?±?0.43 to 34.30?±?8.90 (dextran) and 805.80?±?5.30 (PEG) 24?h after polymer addition. In vitro release profiles showed significantly (p?<?0.05) reduced AUC_{0–8 h}, k and percentage of drug released from two-phase systems compared to β-glucan dispersions, with the PEG system resulting in the lowest amount released over 8?h (15.1?±?1.6%).

Discussion: The unfavorable mixing enthalpy and higher water affinity of PEG resulted in the formation of a dense β-glucan gel.

Conclusion: 1.5% (w/w) β-glucan combined with PEG at a ratio of 1:3 seemed to be the most promising injectable formulation with respect to fastest gel formation, increased hardness and sustained release.     

In vitro release and diffusion studies of promethazine hydrochloride from polymeric dermatological bases using cellulose membrane and hairless mouse skin

The study was designed to investigate the feasibility of developing a transdermal drug dosage form of promethazine hydrochloride (PMH). The in vitro release and diffusion characteristics of PMH from various dermatological polymeric bases were studied using cellulose membrane and hairless mouse skin as the diffusion barriers. These included polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC), cross-linked microcrystalline cellulose, and carboxyl methyl cellulose sodium (Avicel CL-611), and a modified hydrophilic ointment USP. In addition, the effects of several additive ingredients known to enhance the drug release from topical formulations were evaluated. The general rank order for the drug release from these formulations using cellulose membrane was observed to be PEG > HMPC > Avicel CL-611 > hydrophilic ointment base. The inclusion of the additives had little or no effect on the drug diffusion from these bases, except for the hydrophilic ointment formulation containing 15% ethanol, which provided a significant increase in the drug release. However, when these formulations were studied for drug diffusion through the hairless mouse skin, the Avicel CL-611 base containing 15% ethanol exhibited the optimum drug release. The data also revealed that this formulation gave the highest steady-state flux, diffusion, and permeability coefficient values and correlated well with the amount of drug release.     

Development of Local Injectable Dental Gel: The Influence of Certain Additives on Physicochemical Properties of Glycerylmonooleate‐Based Formulations

The current research study is based on the design and development of a sol‐gel biodegradable controlled‐release formulation for use in the treatment of periodontal diseases. Glycerylmonooleate (GMO) was used as a main composition in the gel base. The influence of various additives, e.g., glycerylmonostearate (GMS), methylcellulose (MC), surfactants, and triglycerides, in GMO formulations on rheologic and swelling properties and release characteristics was described. It was demonstrated that the surfactants and triglycerides affected rheologic behavior, whereas GMS and MC influenced both rheologic and swelling properties of the bases. The release study revealed that drug released from the gel bases depended on the square root of time. The kinetics can be explained by the Higuchi's diffusion theory. Some polyols could enhance drug release from the gel. The stability results suggested that the dental gels obtained should be kept in the low temperature range.     

Novel films for drug delivery via the buccal mucosa using model soluble and insoluble drugs

Bioadhesive buccal films are innovative dosage forms with the ability to adhere to the mucosal surface and subsequently hydrate to release and deliver drugs across the buccal membrane. This study aims to formulate and characterize stable carrageenan (CAR) based buccal films with desirable drug loading capacity. The films were prepared using CAR, poloxamer (POL) 407, various grades of PEG (plasticizer) and loaded with paracetamol (PM) and indomethacin (IND) as model soluble and insoluble drugs, respectively. The films were characterized by texture analysis, thermogravimetric analysis (TGA), DSC, scanning electron microscopy, X-ray powder diffraction (XRPD), and in vitro drug release studies. Optimized films were obtained from aqueous gels comprising 2.5% w/w κ-CAR 911, 4% w/w POL 407 and 6% w/w (PM) and 6.5% w/w (IND) of PEG 600 with maximum drug loading of 1.6% w/w and 0.8 % w/w for PM and IND, respectively. TGA showed residual water content of approximately 5% of films dry weight. DSC revealed a T(g) at 22.25 and 30.77°C for PM and IND, respectively, implying the presence of amorphous forms of both drugs which was confirmed by XRPD. Drug dissolution profiles in simulated saliva showed cumulative percent release of up to 45 and 57% of PM and IND, respectively, within 40?min of contact with dissolution medium simulating saliva.