Formulation and Characterization of Risperidone Sustained Release Buccal Tablets using Natural Polymers

Psychotic Disorders

Mental disorders have become highly prevalent due to ambitious lifestyle, urbanization, and stressful environment. Psychosis is a one of the most debilitating, complex, and costly illness. The meaning of “psyche” is mind or soul, and word “-osis” corresponds to an abnormal condition in Greek. Hence, psychosis is often described as involving a “loss of contact with reality.” These illnesses alter a person’s ability to think clearly, make good judgments, respond emotionally, communicate effectively, understand reality, and behave appropriately. Positive symptoms refer to a loss of contact with reality and comprise of hallucinations, delusions, bizarre behavior, and positive formal thought disorders. Negative symptoms refer to a diminution in or absence of normal behaviors and include flat affect, alogia, avolition, and anhedonia. Cognitive symptoms manifest as deficits in attention, learning, memory, concentration, and executive functions (abstract thinking, problem solving) (Parle and Sharma, 2013).

Epidemiology

Retrospectively, about one third (32%) of first episode psychosis cases are not preceded by attenuated psychotic symptoms and may have a sudden onset. A diagnosis of ICD-10 ATPD is made in 19% of patients with a first episode psychosis (10% in developing countries); its reported incidence ranges from 3.9 in the UK to 9.6 in Denmark per 100 000 population per year (the global meta-analytical incidence of all psychotic disorders is 26.6 per 100 000 person-years, 95% CI 22 to 31.7) (Shah et al., 2017). Brief psychotic episodes have been reported to be more common in developing than in developed countries. The ICD-11 Panel indicated that APDD is the most common presentation. However, in our previous meta- analysis only about one third (27.6%, 95%CI 21.0%-35.3%) of ICD-10 ATPD were APDD without symptoms of schizophrenia. In real-world clinical care, clinicians most frequently (71%) diagnose residual classes of ‘other’ or ‘unspecified’ ICD-10 ATPD. APDD without schizophrenia symptoms (ICD-11 ATPD) accounts for only 4% of first-episode psychosis. Further research is needed to test whether the changes introduced by the ICD-11 reduce the incidence and prevalence (and clinical use) of this new category. BPD has been found in 2- 7% of cases of first-onset psychotic disorder, its incidence has not been formally investigated. Because BLIPS/BIPS are defined in help-seeking CHR-P individuals, their incidence in the general non-helpseeking population is not estimable (Fusar et al., 2016).

Pathophysiology

Most strongly linked to the pathophysiology of psychotic disorders is the neurotransmitter dopamine. The positive symptoms of psychotic disorders are believed to be caused by excess dopamine in the mesolimbic tract. Glutamate, an excitatory neurotransmitter, is also implicated. Multiple studies have found a decreased function of the N-methyl-D-aspartate (NMDA) glutamate receptor (Kehrer et al., 2008). Studies have also pointed to gamma-amino-butyric acid (GABA), an important inhibitory neurotransmitter. Some studies show evidence of dysfunction in patients with subjects with schizophrenia. Lastly, implications point to an imbalance in acetylcholine. This finding developed while observing the smoking behaviors of patients with schizophrenia, as nicotine has been shown to increase acetylcholine function. Observers noted some improvements in deficits in the smokers, and cognition was improved in studies as well (Potasiewicz et al., 2017).

Classification of psychotic disorder:

Acute and chronic organic brain syndromes (Cognitive Disorder):

Such as delirium and dementia with psychotic features, some toxic or pathological basis can often be defined. Prominent features are confusions, disorientation, defective memory, disorganized thought and behaviour.

Functional disorder: No underling cause can be defined, memory and orientation are mostly retained but emotion, thought, reasoning and behaviour are seriously altered.

Schizophrenia (Split Mind): Schizophrenia is characterized by delusion, hallucination and lack of insight. Acute schizophrenia may also present with disturbed behaviour, disturbed thinking, or with insidious social withdrawal and other so called negative symptoms and less obvious delusion and hallucination.

• There is no anatomical and pathological defect in the brain.
• Psychosis is due to functional impairment of the brain.
• The cognition is not impaired.

Paranoid States: Paranoid States with marked persecutory or other kinds of fixed delusion (false beliefs) and loss of insight in to the abnormality. About one third of patients suffers from this type and are characterized by presence of delusion and hallucinations. However, there is no thought disorder and no incoherent thinking.

Literature Review:

Ghanma et al., (2024) focused on the development of RIS nanocrystals (NCs), for the first time, which were incorporated into dissolving microneedle array patches (DMAPs) to facilitate the drug delivery of Risperidone (RIS). Ex vivo results showed that 1.16 ± 0.04 mg of RIS was delivered to both the receiver compartment and full-thickness skin from NCs loaded DMAPs compared to 0.75 ± 0.07 mg from bulk RIS DMAPs.

Medarametla et al., (2024) assessed the sustained-release matrix tablets containing Valsartan, an angiotensin II receptor type 1 antagonist. Notably, formulations F4 and F7 demonstrated promising dissolution profiles, effectively controlling the release of the drug. These formulations, enriched with higher concentrations of chitosan and sodium alginate in addition to other polymers, successfully sustained the drug release for the entire 24-hour duration.

Yahoum et al., (2023) showed the drug release studies complete metformin hydrochloride release from the beads, especially those prepared from xanthan gum at the concentration of 1.25%, in intestinal medium at 90.00% after 6 h. However, limited and insignificant drug release was observed within the gastric medium (32.50%). The dissolution profiles showed sustained release kinetics.

Kabir et al., (2023) optimized formulation of sustained release tablet dosage form of Diacerein that will be highly patient compliant. A three-level full factorial design was employed to develop nine different formulations of matrix tablets using a combination of Methocel K100M CR and Methocel K4M CR polymer at different ratios. The physical evaluation of both the drug-excipient powder mixtures and tablets of the nine formulations were performed and results were found to be within acceptable ranges for all tests.

Kumar et al., (2023) observed that this method significantly increased these properties compared to pure drug. Atorvastatin calcium tablets were examined for appearance, disintegration speed, drug release, average weight, weight variability, thickness, diameter, and hardness. The tablets' formulation complied with all Pharmacopoeia requirements.When the drug release profiles of all batches were compared to those of the innovator tablet.

Jabar and Alhammid, (2022) improved solubility and dissolution of risperidone by preparing nanosuspension using different stabilizers and different solvents in a method known as solvent-antisolvent precipitation method. Twenty-eight formulas were prepared and evaluated particle size, PDI, (EE), zeta potential, and in-vitro dissolution studies. The best formula (F13) has particle size (40.9) nm containing a (Soluplus) as a stabilizer in ratio 1:1 with drug by using acetone as a solvent in ratio 1:5 with water which was act as anti- solvent with stirring speed 1000 rpm and E.E % was 98.

Shukla et al., (2022) used xanthan gum (xg), tamarind gum (TG), and fenugreek gum to create a sustained release matrix tablet of nifedipine (NFD). For the dissolution rate study, 0.1N HCl pH 1.2 was used for two hours, followed by 12 hours in phosphate buffer pH 6.8. We observed and took note of the effects of three different polymer concentrations as well as polymer blend concentration. Using the Higuchi expression, the data on dissolution was examined.

Experimental Work and Result:

Solubility Analysis

A qualitative determination of the solubility was made by adding solvent in small incremental amount to a test tube containing fixed quantity of solute or vice versa. After each addition, the system was vigorously shaken and observed visually (Indian pharmacopeia, 2007).

Table 1: Qualitative solubility studies of Risperidone

Fourier transform infrared spectroscopy (FTIR)

Infrared spectrum of any compound given information about the functional group present in particular compound. An infrared spectrum of drug was taken using KBr pellet method. Various peaks in IR spectrum were interpreted for presence of different group in the structure of drug (Lachman et al., 2008). The IR spectrum was recorded on FTIR spectrophotometer and represented in Figure 7.1.

Figure 1: FT-IR spectra of standard Risperidone

Table 2: FT-IR interpretation of Risperidone

UV – Spectroscopic Analysis

UV spectroscopic analysis method is another “Absorption Spectrometry Method”. In this analysis the sample was placed in front of UV rays. Characteristic peaks of FTIR spectra of Risperidone sample of light i.e. known as “Absorption Maxima (λ_max)” which lies in the range of 200-400 nm undergo transition from ground state to excited state and this particular phenomenon creates a particular UV-absorption spectrum curve (Gibson, 2001). This λ_max is characteristic feature of a particular compound and give the valuable information regarding about the “Qualitative and Quantitative aspect” in accordance with “Beer’s-Lambert’s law.

Figure 2: UV Scan of standard Risperidone