Pharmaceutical Formulation And In Vitro Evaluation of Ambroxol Hydrochloride Fast Dissolving Sublingual Films

The oral route is the most preferred method of drug administration because of its convenience, non-invasive nature, and improved patient compliance. However, paediatric, geriatric, and dysphagic patients often experience difficulty in swallowing conventional dosage forms, leading to poor compliance and ineffective therapy.[1] To overcome these limitations, fast-disintegrating dosage forms were developed as an alternative to conventional tablets and capsules, as they rapidly disintegrate in the oral cavity without the need for water and improve patient convenience.[2]

The sublingual route was employed to achieve rapid systemic drug delivery and is particularly beneficial for patients with swallowing difficulties. Drugs administered beneath the tongue are absorbed directly into the systemic circulation through the highly vascularized sublingual mucosa, partially bypassing hepatic first-pass metabolism and improving bioavailability.[3] The sublingual region exhibits greater permeability because of its thin, non-keratinized epithelium and rich blood supply.[4] Drug absorption through this route is mainly influenced by lipid solubility, degree of ionization, and molecular weight and occurs predominantly by passive diffusion across the mucosal membrane.[5] In addition, factors such as salivary flow, residence time in the oral cavity, and drug lipophilicity significantly affect sublingual drug absorption.[6]

Fast dissolving sublingual films are thin, flexible polymeric strips that rapidly hydrate and disintegrate in saliva, releasing the drug for absorption through the oral mucosa.[7] These films provide several advantages, including rapid onset of action, ease of administration without water, improved patient compliance, and enhanced bioavailability.[8]

Ambroxol Hydrochloride is a well-established mucolytic and expectorant agent widely used in the management of respiratory disorders such as bronchitis, chronic obstructive pulmonary disease, and asthma. It enhances mucociliary clearance by reducing mucus viscosity and increasing surfactant production. However, conventional dosage forms are associated with limitations such as delayed onset of action, first-pass metabolism, and reduced patient compliance, particularly in paediatric and geriatric patients.[9]

Therefore, the present study was undertaken to formulate and evaluate fast dissolving sublingual films of Ambroxol Hydrochloride using suitable film-forming polymers and excipients to achieve rapid drug release and improved therapeutic efficacy.

MATERIALS USED

Ambroxol Hydrochloride was purchased from Balaji drug store., Mumbai, PEG 4000 collected from Central Drug House Pvt Ltd., New Delhi, HPMC E15 LV from Loba Chemie Pvt Ltd., Mumbai, CCS and Aspartame from Shreeji Chemicals., Mumbai, PEG 400 from Ranbaxy Laboratories Ltd., Punjab, PVA, Citric acid and Menthol from SD Fine Chem Ltd., Mumbai.

PREFORMULATION STUDIES

The Ambroxol hydrochloride pure drug was evaluated for different parameters like determination of melting point, solubility analysis, determination of absorption maximum (λmax), standard calibration curve, drug and excipient interaction by FTIR.

Determination of melting point of the drug

The melting point of Ambroxol Hydrochloride was determined using the capillary tube method with the aid of a melting point apparatus. [10]

Determination of absorption maximum (λmax) of the drug

A solution of Ambroxol Hydrochloride with a concentration of 10 µg/mL was prepared using phosphate buffer (pH 6.8): methanol (1:1). The prepared solution was scanned in the wavelength range of 200–400 nm using a UV-Visible spectrophotometer to determine the wavelength of maximum absorption (λmax). The absorption spectrum obtained was used to identify the λmax of Ambroxol Hydrochloride.[11]

Fourier transform infrared spectroscopy (FTIR) studies

FTIR studies were carried out to investigate the compatibility between Ambroxol Hydrochloride and the selected excipients. The infrared spectra of pure Ambroxol Hydrochloride and its physical mixtures with PEG 4000, HPMC E15, Polyvinyl Alcohol (PVA), Cross Carmellose Sodium (CCS), PEG 400, Aspartame and Citric acid were recorded over a spectral range of 3500–800 cm⁻¹ using a Shimadzu IR Spirit FTIR spectrophotometer.[12]

METHOD OF PREPARATION

Solvent Casting Technique

Solvent casting method is one of the simplest and most widely employed techniques for film formulation. This method offers better film clarity and uniform thickness compared to extrusion methods. In this technique, the required quantity of polymers is dissolved in distilled water, while the drug solid dispersion and other excipients were dissolved in a suitable solvent system. Both solutions are then combined and stirred continuously to obtain a homogeneous mixture known as the casting solution. The resulting solution is poured into a casting mould or Petri dish and allowed to dry by solvent evaporation, resulting in the formation of films. [13]

Preparation of Fast Dissolving Sublingual Films

The fast dissolving sublingual films of Ambroxol Hydrochloride were prepared by the solvent casting method. Initially, the required quantities of the film-forming polymers, HPMC E15 and Polyvinyl Alcohol (PVA), were accurately weighed and dissolved in distilled water. The polymeric solution was allowed to stand for 15 minutes to ensure complete hydration and swelling of the polymers and was then stirred on a magnetic stirrer for 30 minutes to obtain a clear and bubble-free solution.[14]

In a separate beaker, the required quantity of Ambroxol Hydrochloride solid dispersion was dissolved in a suitable solvent system and stirred continuously until a clear solution was obtained. PEG 400 was added as a plasticizer, while Cross Carmellose Sodium (CCS), Aspartame, Citric acid, Menthol and Peppermint oil were incorporated into the formulation with continuous stirring. The drug solution and polymeric solution were then mixed thoroughly using a magnetic stirrer to obtain a homogeneous casting solution.

The resulting solution was poured into a pre-lubricated glass Petri plate and dried at room temperature until a flexible film was formed. After complete drying, the films were carefully peeled off and cut into 2 × 2 cm² pieces. The prepared films were wrapped in butter paper and aluminium foil and stored at room temperature until further evaluation.[15]

 

 

Figure 1: λmax of Ambroxol Hydrochloride

 

 

Figure 2: FT-IR Spectra of Ambroxol Hydrochloride.

 

 

Figure 3: FTIR Spectra of Ambroxol Hydrochloride and physical mixture (PEG 4000, HPMC E 15, PVA, CCS, PEG 400, Aspartame, Citric acid)

 

 

Figure 4: Thickness of formulations F1-F6

 

 

Figure 5: Weight variation of formulations F1-F6

 

 

Figure 6: Surface pH of formulations F1-F6

 

 

Figure 7: Drug content of formulations F1-F6

 

 

Figure 8: % Cumulative drug release of formulation F1-F6

CONCLUSION

The present study successfully formulated and evaluated Ambroxol Hydrochloride fast dissolving sublingual films by the solvent casting method. The prepared films exhibited satisfactory physicochemical and mechanical characteristics and showed rapid drug release within a short duration, indicating their suitability for sublingual administration. Among all the formulations, F5 demonstrated the best overall performance with the highest drug content, maximum drug release, excellent folding endurance and acceptable physicochemical characteristics and was therefore selected as the optimized formulation. Hence, the developed fast dissolving sublingual film of Ambroxol Hydrochloride can be considered a promising dosage form for achieving rapid systemic drug delivery and onset of action.

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